Updated on 2025/09/18

写真a

 
SASAKI Takashi
 
Organization
School of Medicine Animal Research Center Lecturer
Title
Lecturer
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Degree

  • 博士(医学) ( 順天堂大学大学院医学研究科感染制御科学 )

Research Interests

  • ゲノム進化

  • 哺乳類

  • 共進化

  • 感染症

  • ブドウ球菌

  • メタゲノム

  • 糞便移植

  • 潰瘍性大腸炎

  • 猫伝染性腹膜炎

  • 肥満細胞腫

  • MRSA

  • MRSP

  • 獣医微生物学

  • マイクロバイオーム

  • イヌ細菌性膿皮症

  • 薬剤耐性

Research Areas

  • Life Science / Genome biology

  • Life Science / Laboratory animal science

  • Life Science / Biodiversity and systematics

  • Life Science / Veterinary medical science

  • Life Science / Bacteriology

Education

  • Juntendo University   Graduate School of Medicine

    2006.4 - 2009.3

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Research History

  • Sapporo Medical University   School of Medicine, Animal Experimentation Center   Lecturer

    2017.5

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  • Juntendo University   Faculty of Medicine   Assistant Professor

    2014.4 - 2017.4

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  • Nippon Veterinary and Life Science University   Faculty of Veterinary Science

    2013.8 - 2014.3

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  • 国立感染症研究所   病原体ゲノム解析研究センター   日本学術振興会特別研究員PD

    2011.4 - 2013.7

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  • Juntendo University   Graduate School of Medicine

    2009.4 - 2011.3

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  • 東京都内動物病院   獣医師

    2004.4 - 2005.12

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Professional Memberships

  • 日本実験動物学会

    2020.4

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  • 公私立大学実験動物施設協議会

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  • 日本ブドウ球菌研究会

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  • JAPANESE SOCIETY FOR BACTERIOLOGY

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  • THE JAPANESE SOCIETY OF VETERINARY SCIENCE

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Committee Memberships

  • 公私立大学実験動物施設協議会(公私動協)   バイオセーフティ委員会 委員長  

    2020.4   

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  • 日本実験動物学会   実験動物感染症対策委員会 委員  

    2020.4   

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  • 日本細菌学会 北海道支部会   幹事  

    2017.5   

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  • 公私立大学実験動物施設協議会(公私動協)   バイオセーフティー委員会 委員  

    2017.5 - 2020.3   

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  • 日本獣医皮膚科学会   犬の膿皮症治療ガイドライン策定に向けた学会推進研究班 班長  

    2017.4   

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  • 日本獣医皮膚科学会   犬の膿皮症;治療ガイドライン小委員会 委員  

    2014.4 - 2016.3   

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Papers

  • Near-complete genome sequencing of the feline coronavirus serotype I strain FIPV-Aqua from a cat with feline infectious peritonitis in Japan. Reviewed International journal

    Yoshikazu Tanaka, Eri Tanabe, Takashi Sasaki

    Microbiology resource announcements   14 ( 6 )   e0035725   2025.6

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    Feline coronavirus causes the fatal disease feline infectious peritonitis (FIP), for which no effective vaccine is currently available. Here, we present the near-complete genome sequence of the Japanese strain FIPV-Aqua.

    DOI: 10.1128/mra.00357-25

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  • Emergence of community-associated methicillin-resistant Staphylococcus aureus ΨUSA300 among Japanese people with HIV, resulted from stepwise mutations in 2010s. Reviewed International journal

    Koh Shinohara, Yuki Uehara, Katsuji Teruya, Takashi Sasaki, Tadashi Baba, Hidemasa Nakaminami, Pegah Kananizadeh, Yuh Morimoto, Yoshimi Kikuchi, Shinichi Oka

    Scientific reports   13 ( 1 )   8322 - 8322   2023.5

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    Although infection with the methicillin-resistant Staphylococcus aureus (MRSA) clone USA300 is extremely rare in Japan, the uniquely evolved clone ΨUSA300 has been reported in Japan. An outbreak of a distinct USA300 clone was recently reported in an HIV/AIDS referral hospital in Tokyo. The present study investigated the evolutionary origin and genetic diversity of USA300-related clones causing regional outbreaks among people living with HIV (PLWHIV) in Tokyo. MRSA isolates collected from PLWHIV in an HIV/AIDS referral center in Tokyo were subjected to whole-genome sequencing and their genetic features were compared with those of previously described USA300 MRSA genomes. Of the 28 MRSAs isolated in 2016-2019, 23 (82.1%) were identified as USA300, with 22 (95.6%) of the latter identified as ΨUSA300. Although the genomic structure of ΨUSA300 was identical to the structures of reference USA300 strains, one clade (cluster A) was found to have acquired 29 previously identified lineage-specific mutations in a stepwise manner. The estimated divergence dates of ΨUSA300 and Cluster A were 2009 and 2012, respectively. These findings suggested that the ΨUSA300 clone had spread among PLWHIVs in Tokyo in the early 2010s, with stepwise acquisition of lineage-specific nonsynonymous mutations.

    DOI: 10.1038/s41598-023-35171-y

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  • Complete Genome Sequencing of a Community-Associated Methicillin-Resistant Staphylococcus aureus ψUSA300 Strain JICS127, a Uniquely Evolved USA300 Lineage in Japan. Reviewed International journal

    Koh Shinohara, Tadashi Baba, Takashi Sasaki, Katsuji Teruya, Yuki Uehara

    Microbiology resource announcements   11 ( 9 )   e0071722   2022.9

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    A ψUSA300 clone of MRSA, a derivative of USA300, is uniquely found in Japan and has 12-bp deletion on ccrB2 in type IVa staphylococcal cassette chromosome mec element. We hereby present the complete genome of ψUSA300 strain JICS127.

    DOI: 10.1128/mra.00717-22

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  • Genetic and phenotypic diversity of methicillin-resistant Staphylococcus aureus among Japanese inpatients in the early 1980s. Reviewed International journal

    Hui Zuo, Yuki Uehara, Yujie Lu, Takashi Sasaki, Keiichi Hiramatsu

    Scientific reports   11 ( 1 )   5447 - 5447   2021.3

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    To trace the linkage between Japanese healthcare-associated methicillin-resistant Staphylococcus aureus (HA-MRSA) strains in the early 1980s and the 2000s onward, we performed molecular characterizations using mainly whole-genome sequencing. Among the 194 S. aureus strains isolated, 20 mecA-positive MRSA (10.3%), 8 mecA-negative MRSA (4.1%) and 3 mecA-positive methicillin-susceptible S. aureus (MSSA) (1.5%) strains were identified. The most frequent sequence type (ST) was ST30 (n = 11), followed by ST5 (n = 8), ST81 (n = 4), and ST247 (n = 3). Rates of staphylococcal cassette chromosome mec (SCCmec) types I, II, and IV composed 65.2%, 13.0%, and 17.4% of isolates, respectively. Notably, 73.3% of SCCmec type I strains were susceptible to imipenem unlike SCCmec type II strains (0%). ST30-SCCmec I (n = 7) and ST5-SCCmec I (n = 5) predominated, whereas only two strains exhibited imipenem-resistance and were tst-positive ST5-SCCmec II, which is the current Japanese HA-MRSA genotype. All ST30 strains shared the common ancestor strain 55/2053, which caused the global pandemic of Panton-Valentine leukocidin-positive MSSA in Europe and the United States in the 1950s. Conspicuously more heterogeneous, the population of HA-MRSA clones observed in the 1980s, including the ST30-SCCmec I clone, has shifted to the current homogeneous population of imipenem-resistant ST5-SCCmec II clones, probably due to the introduction of new antimicrobials.

    DOI: 10.1038/s41598-021-84481-6

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  • Nicotine Oral Administration Attenuates DSS-Induced Colitis Through Upregulation of Indole in the Distal Colon and Rectum in Mice. Reviewed International journal

    Akihito Nakajima, Tomoyoshi Shibuya, Takashi Sasaki, Yu Jie Lu, Dai Ishikawa, Keiichi Haga, Masahito Takahashi, Naoko Kaga, Taro Osada, Nobuhiro Sato, Akihito Nagahara

    Frontiers in medicine   8   789037 - 789037   2021

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    Nicotine affects the gastrointestinal environment and modulates ulcerative colitis (UC). However, the associations among nicotine, gut metabolites, and UC are still largely unknown. We investigated whether orally administered nicotine affected gut metabolites and dextran sodium sulfate (DSS)-induced colitis. C57BL/6 male mice were orally administered nicotine solution in drinking water prior to inducing DSS-induced colitis. Short-chain fatty acids (SCFAs) and indole in gut contents and fecal samples were measured by GC-MS and hydroxylamine-based indole assays, respectively. Oral administration of nicotine increased indole concentration in feces, but, in contrast, SCFA values did not differ with nicotine administration. Indole levels were increased in the distal colon and rectum but not in the cecum and proximal colon. DSS-induced colitis was less severe clinically and histological changes were minimal in the rectum of orally nicotine-administered mice compared to mice drinking only water. 16S rRNA microbiome on the feces revealed an increasing in Clostridium and Porphyromonas in nicotine-administered mice. In conclusion, nicotine administration was associated with increased indole levels in the distal colon and rectum and attenuated DSS-induced colitis. Oral administration of nicotine may play a potential role in indole upregulation and prevention of UC.

    DOI: 10.3389/fmed.2021.789037

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  • Corynebacterium Species of the Conjunctiva and Nose: Dominant Species and Species-Related Differences of Antibiotic Susceptibility Profiles. Reviewed International journal

    Saichi Hoshi, Daisuke Todokoro, Takashi Sasaki

    Cornea   39 ( 11 )   1401 - 1406   2020.11

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    PURPOSE: Nondiphtherial Corynebacterium species are normal residents of human skin and mucosa, including the conjunctiva and nose, but can cause conjunctivitis and keratitis. Recently, resistance against various classes of antibiotics has been reported in Corynebacterium. The present study investigated the type of species and antibiotic susceptibilities of the conjunctival and nasal Corynebacterium species. METHODS: This study examined 183 strains of Corynebacterium species that were isolated from patients undergoing preoperative examinations for cataract surgery. Species were identified by RNA polymerase β-subunit-encoding gene (rpoB) sequencing. Antibiotic susceptibility tests were performed by the microdilution method according to the Clinical and Laboratory Standards Institute standard method M45. RESULTS: Corynebacterium macginleyi was the most predominant species (84%; 46 of 55) in the conjunctiva. The 2 major species in the nasal cavity were Corynebacterium accolens and Corynebacterium propinquum (44% and 31%, respectively), followed by Corynebacterium pseudodiphtheriticum (8%), Corynebacterium jeikeium (7%), and C. macginleyi (3%). In contrast to other nasal Corynebacterium species, only C. macginleyi showed a high susceptibility to macrolides. However, among nonconjunctival Corynebacterium species, C. propinquum, was unique in having a high resistance rate to levofloxacin (29%), comparable with that observed in C. macginleyi (36%). Penicillin G and tobramycin showed good susceptibility in almost all strains. CONCLUSIONS: Drug resistance against fluoroquinolones and macrolides was observed in Corynebacterium species, with the antibiotic susceptibility profiles correlating with differences of the species and niche. Nasal and conjunctival Corynebacterium profiles of drug resistance suggest habitat segregation strictly at the species level.

    DOI: 10.1097/ICO.0000000000002445

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  • An outbreak of USA300 MRSA among people with HIV in Japan. Reviewed International journal

    Kazuhiko Ikeuchi, Eisuke Adachi, Takashi Sasaki, Masato Suzuki, Lay Ahyoung Lim, Makoto Saito, Michiko Koga, Takeya Tsutsumi, Yasutoshi Kido, Yuki Uehara, Hiroshi Yotsuyanagi

    The Journal of infectious diseases   223 ( 4 )   610 - 620   2020.10

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    BACKGROUND: USA300 produces Panton-Valentin leucocidin (PVL), and is known as a predominant community-associated methicillin-resistant Staphylococcus aureus (MRSA) strain in the United States, but it was extremely rare in Japan. We report here an outbreak of USA300 in people with HIV (PWH) in Tokyo, Japan. METHODS: We analyzed the cases of PVL-MRSA infection between 2010 and 2020 and screened for nasal colonization of PVL-MRSA in PWH who visited an HIV/AIDS referral hospital from December 2019 to March 2020. Whole-genome sequencing (WGS)-based single nucleotide polymorphism (SNP) analysis was performed for these isolates. RESULTS: During the study period, a total of 21 PVL-MRSA infections in 14 patients were identified after 2014. The carriage prevalence was 4.3% (12/277), and PVL-MRSA carriers were more likely to have sexually transmitted infections (STIs) within a year compared with patients who had neither the history of PVL-MRSA infection nor colonization (33.3% [4/12] vs 10.1% [26/258], P=0.03). SNP analysis showed that all 26 isolates were ST8-SCCmecⅣa-USA300. Twenty-four isolates were closely related (≤100 SNP differences) and had the nonsynonymous SNPs associated with carbohydrate metabolism and antimicrobial tolerance. CONCLUSIONS: An outbreak of USA300 has been occurring among PWH in Tokyo, and a history of STI was a risk of colonization.

    DOI: 10.1093/infdis/jiaa651

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  • RNA Sequencing Identifies a Common Physiology in Vancomycin- and Ciprofloxacin-Tolerant Staphylococcus aureus Induced by ileS Mutations. Reviewed International journal

    Madhuri Singh, Miki Matsuo, Takashi Sasaki, Tomomi Hishinuma, Norio Yamamoto, Yuh Morimoto, Teruo Kirikae, Keiichi Hiramatsu

    Antimicrobial agents and chemotherapy   64 ( 10 )   2020.9

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    Little is known about the mechanisms by which ileS mutations induce vancomycin tolerance in Staphylococcus aureus This study showed that transcriptome profiles were similar in vancomycin-tolerant mutants and the IleRS-inhibitor-treated parent. Notably, ileS and relA, which induce a stringent response, were upregulated. The same mechanism was responsible for cross-tolerance to vancomycin and ciprofloxacin. These findings suggest that the accumulation of uncharged isoleucyl-tRNA following ileS mutations in S. aureus was responsible for drug tolerance.

    DOI: 10.1128/AAC.00827-20

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  • Epidemiology of methicillin-resistant Staphylococcus aureus in a Japanese neonatal intensive care unit. Reviewed International journal

    Atsushi Tsujiwaki, Ken Hisata, Yudai Tohyama, Nobuaki Matsunaga, Yuki Uehara, Takashi Sasaki, Keiichi Hiramatsu, Toshiaki Shimizu

    Pediatrics international : official journal of the Japan Pediatric Society   62 ( 8 )   911 - 919   2020.8

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    BACKGROUND: There have been few reports on the genetic structure of the current population of methicillin-resistant Staphylococcus aureus (MRSA) from neonatal intensive care units (NICUs) in Japan. In the present study we conducted a molecular epidemiological analysis based on whole genome sequencing against MRSA strains in a Japanese NICU. METHODS: We performed genotyping by whole genome sequencing, polymerase chain reaction-based typing of Staphylococcal cassette chromosome mec (SCCmec) and polymerase chain reaction-based open-reading frame typing against 57 MRSA strains from fecal or nasal specimens from NICU patients in Juntendo University Shizuoka Hospital in 2013-2014. RESULTS: Forty-nine MRSA strains (86.0%) exhibited a clonal complex (CC) 1, and were divided into three sequence types (STs): ST2725 (n = 25), ST2764 (n = 21), and ST1 (n = 3). All CC1 MRSA strains had SCCmec IVa, and were resistant to new quinolones, which are limited in pediatric use, suggesting that these strains were derived from adult MRSA clones. Single nucleotide polymorphism differences of both ≤10 and >100 nucleotides were observed by pairwise, single nucleotide polymorphism analysis among ST2725 and ST2764 MRSA strains, respectively. Seven ST8 MRSA strains (12.2%) were isolated, and no strain exhibiting the Japanese hospital-associated MRSA genotype (ST5/SCCmec II) was isolated in this study. CONCLUSIONS: Our molecular epidemiological analysis suggested that ST2725 and ST2764 MRSA strains had genetic diversity that could not be explained only by a recent transmission event in the NICU. These MRSA clones might be disseminated in other Japanese hospital facilities as new endemic clones. Our results are expected to contribute to the improvement of infection control measures of MRSA in NICUs.

    DOI: 10.1111/ped.14241

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  • A Soluble Fiber Diet Increases Bacteroides fragilis Group Abundance and Immunoglobulin A Production in the Gut. Reviewed International journal

    Akihito Nakajima, Takashi Sasaki, Kikuji Itoh, Takashi Kitahara, Yoshinori Takema, Keiichi Hiramatsu, Dai Ishikawa, Tomoyoshi Shibuya, Osamu Kobayashi, Taro Osada, Sumio Watanabe, Akihito Nagahara

    Applied and environmental microbiology   86 ( 13 )   2020.6

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    Immunoglobulin A (IgA) is essential for defense of the intestinal mucosa against harmful pathogens. Previous studies have shown that Bacteroidetes, the major phylum of gut microbiota together with Firmicutes, impact IgA production. However, the relative abundances of species of Bacteroidetes responsible for IgA production were not well understood. In the present study, we identified some specific Bacteroidetes species that were associated with gut IgA induction by hsp60-based profiling of species distribution among Bacteroidetes The levels of IgA and the expression of the gene encoding activation-induced cytidine deaminase (AID) in the large intestine lamina propria, which is crucial for class switch recombination from IgM to IgA, were increased in soluble high-fiber diet (sHFD)-fed mice. We found that Bacteroides acidifaciens was the most abundant Bacteroidetes species in both sHFD- and normal diet-fed mice. In addition, the gut IgA levels were associated with the relative abundance of Bacteroides fragilis group species such as Bacteroides faecis, Bacteroides caccae, and Bacteroides acidifaciens Conversely, the ratio of B. acidifaciens to other Bacteroidetes species was reduced in insoluble high-fiber diet fed- and no-fiber diet-fed mice. To investigate whether B. acidifaciens increases IgA production, we generated B. acidifaciens monoassociated mice and found increased gut IgA production and AID expression. Collectively, soluble dietary fiber increases the ratio of gut Bacteroides fragilis group, such as B. acidifaciens, and IgA production. This might improve gut immune function, thereby protecting against bowel pathogens and reducing the incidence of inflammatory bowel diseases.IMPORTANCE Immunoglobulin A (IgA) is essential for defense of the intestinal mucosa against harmful pathogens. Gut microbiota impact IgA production, but the specific species responsible for IgA production remain largely elusive. Previous studies have shown that IgA and Bacteroidetes, the major phyla of gut microbiota, were increased in soluble high-fiber diet-fed mice. We show here that the levels of IgA in the gut and the expression of activation-induced cytidine deaminase (AID) in the large intestine lamina propria, which is crucial for class switch recombination from IgM to IgA, were correlated with the abundance of Bacteroides fragilis group species such as Bacteroides faecis, Bacteroides caccae, and Bacteroides acidifaciensB. acidifaciens monoassociated mice increased gut IgA production and AID expression. Soluble dietary fiber may improve gut immune function, thereby protecting against bowel pathogens and reducing inflammatory bowel diseases.

    DOI: 10.1128/AEM.00405-20

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  • Genetic alterations of KIT during clonal expansion and subsequent acquisition of resistance to toceranib in a canine mast cell tumor cell line. Reviewed International journal

    Sena Kurita, Ryo Miyamoto, Hiroyuki Tani, Masato Kobayashi, Takashi Sasaki, Kyoichi Tamura, Makoto Bonkobara

    Journal of veterinary pharmacology and therapeutics   42 ( 6 )   673 - 681   2019.11

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    One of the potential mechanisms underlying acquired resistance to toceranib in canine mast cell tumor (MCT) is the emergence of a secondary mutation in the KIT gene. Here, genetic alterations of KIT during clonal expansion and subsequent acquisition of resistance to toceranib were investigated in the toceranib-susceptible canine MCT cell line VI-MC, which carries a KIT-activating mutation resulting in a predicted p.(Asn508Ile) amino acid change in the receptor tyrosine kinase protein KIT. Two sublines were cloned from VI-MC and toceranib-resistant sublines then were established by continuous exposure to toceranib. The mutation status of KIT in parental VI-MC and its sublines was investigated using next-generation sequencing (NGS). Additionally, effects of secondary mutations on toceranib sensitivity in p.(Asn508Ile)-mutant KIT were examined. KIT secondary mutations, including those encoding p.(Asn679Lys)-, p.(Asp819Val)-, and p.(Asp819Gly)-mutant KIT, that confer toceranib insensitivity to p.(Asn508Ile)-mutant KIT emerged only in toceranib-resistant VI-MCs. These mutations were not detected by NGS in the parental VI-MC line or in the toceranib-naive cloned VI-MCs, although the parental line and sublines exhibited genetic heterogeneity in KIT that may have been caused by genetic evolution during clonal expansion. VI-MC clones with these secondary mutations in KIT appear to have arisen from subclones during treatment with toceranib rather than being pre-existing. However, further study using a higher resolution technique will be needed to confirm the developmental mechanism of KIT secondary mutation in canine MCT cells with acquired resistance to toceranib.

    DOI: 10.1111/jvp.12816

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  • A genetic variant of CYP2R1 identified in a cat with type 1B vitamin D-dependent rickets: a case report. Reviewed International journal

    Takahiro Teshima, Sena Kurita, Takashi Sasaki, Hirotaka Matsumoto, Ayaka Niina, Daijiro Abe, Nobuo Kanno, Hidekazu Koyama

    BMC veterinary research   15 ( 1 )   62 - 62   2019.2

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    BACKGROUND: Vitamin D-dependent rickets is rare in animals and humans. Several types of this condition are associated with genetic variants related to vitamin D metabolism. This is the first report of type 1B vitamin D-dependent rickets in a cat. CASE PRESENTATION: Here, we describe the case of a 3-month-old female domestic short-haired cat previously fed on commercial kitten food that presented at our clinic with seizures, lethargy, and generalized pain. Serum and ionized calcium concentrations and 1,25-dihydroxycholecalciferol in this cat were low, and radiographs showed skeletal demineralization and abnormally wide growth plates on the long bones. Initially, simple vitamin D deficiency was suspected; however, the cat's profile, which included fed a well-balanced commercial diet, together with the findings of additional laboratory tests and the cat's unresponsiveness to various treatments, raised the suspicion of vitamin D-dependent rickets. Examination of the DNA sequences of CYP2R1 and CYP27B1 genes, which are genes linked with vitamin D metabolism, showed a CYP2R1 frameshift mutation in exon 5 (where T is deleted at position c.1386). This mutation alters the amino acid sequence from position 462, while the stop codon introduced at position 481 prematurely truncates the 501 amino acid full-length protein. With this knowledge, a new treatment regime based on a standard dose of calcitriol was started and this markedly improved the cat's condition. CONCLUSIONS: To the best of our knowledge, the present case is the first description of type 1B vitamin D-dependent rickets linked with a genetic variant of CYP2R1 in a cat.

    DOI: 10.1186/s12917-019-1784-1

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  • Comparison of USA300 with non-USA300 methicillin-resistant Staphylococcus aureus in a neonatal intensive care unit. Reviewed International journal

    Takemi Murai, Kaoru Okazaki, Kazue Kinoshita, Yuki Uehara, Hui Zuo, Yujie Lu, Yuki Ono, Takashi Sasaki, Keiichi Hiramatsu, Yuho Horikoshi

    International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases   79   134 - 138   2019.2

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    OBJECTIVES: Reports of USA300 methicillin-resistant Staphylococcus aureus (MRSA) strain were still scarce in neonatal intensive care units (NICUs) and the relationship of USA300 MRSA to clinical infections is still controversial. The primary outcome was the incidence of MRSA infections caused by the USA300 and non-USA300 strains at a NICU in Japan. METHODS: This retrospective cohort study was conducted between November 2011 and October 2016 at Tokyo Metropolitan Children's Medical Center in Japan. All MRSA isolated after 48h of hospitalization were included for analysis by pulsed-field gel electrophoresis (PFGE) using the standard USA300 strain. Genes were tested for Panton-Valentine leukocidin (PVL) and arginine catabolic mobile element (ACME). A whole genome sequence was performed for representative isolates of USA300. RESULTS: In total, 109 MRSA isolates were included for analysis. PFGE classified 34 and 75 isolates of USA300 and non-USA300 MRSA, respectively. Both PVL and ACME genes were detected in USA300 and non-USA300 strains at rate of 100% (34/34) and 5.3% (4/75), respectively (P<0.05). There was no statistically significant difference in the proportion of clinical diseases between USA- 300 and non-USA 300 strains. CONCLUSIONS: Infants with USA300 MRSA infection did not differ significantly from those with non-USA300 MRSA infection.

    DOI: 10.1016/j.ijid.2018.11.020

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  • Genetic and Transcriptomic Analyses of Ciprofloxacin-Tolerant Staphylococcus aureus Isolated by the Replica Plating Tolerance Isolation System (REPTIS). Reviewed International journal

    Miki Matsuo, Miyu Hiramatsu, Madhuri Singh, Takashi Sasaki, Tomomi Hishinuma, Norio Yamamoto, Yuh Morimoto, Teruo Kirikae, Keiichi Hiramatsu

    Antimicrobial agents and chemotherapy   63 ( 2 )   e02019 - 18   2019.2

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    We developed a simple, efficient, and cost-effective method, named the replica plating tolerance isolation system (REPTIS), to detect the antibiotic tolerance potential of a bacterial strain. This method can also be used to quantify the antibiotic-tolerant subpopulation in a susceptible population. Using REPTIS, we isolated ciprofloxacin (CPFX)-tolerant mutants (mutants R2, R3, R5, and R6) carrying a total of 12 mutations in 12 different genes from methicillin-sensitive Staphylococcus aureus (MSSA) strain FDA209P. Each mutant carried multiple mutations, while few strains shared the same mutation. The R2 strain carried a nonsense mutation in the stress-mediating gene, relA Additionally, two strains carried the same point mutation in the leuS gene, encoding leucyl-tRNA synthetase. Furthermore, RNA sequencing of the R strains showed a common upregulation of relA Overall, transcriptome analysis showed downregulation of genes related to translation; carbohydrate, fat, and energy metabolism; nucleotide synthesis; and upregulation of amino acid biosynthesis and transportation genes in R2, R3, and R6, similar to the findings observed for the FDA209P strain treated with mupirocin (MUP0.03). However, R5 showed a unique transcription pattern that differed from that of MUP0.03. REPTIS is a unique and convenient method for quantifying the level of tolerance of a clinical isolate. Genomic and transcriptomic analyses of R strains demonstrated that CPFX tolerance in these S. aureus mutants occurs via at least two distinct mechanisms, one of which is similar to that which occurs with mupirocin treatment.

    DOI: 10.1128/AAC.02019-18

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  • Regional outbreak of community-associated methicillin-resistant Staphylococcus aureus ST834 in Japanese children. Reviewed International journal

    Yuki Uehara, Takashi Sasaki, Tadashi Baba, Yujie Lu, Eri Imajo, Yuka Sato, Shigeru Tanno, Munehiro Furuichi, Miki Kawada, Keiichi Hiramatsu

    BMC infectious diseases   19 ( 1 )   35 - 35   2019.1

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    BACKGROUND: Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) infection has recently become a challenging problem worldwide and in Japan. We experienced 10 pediatric patients infected with CA-MRSA and hospitalized from 2011 to 2014 in a tertiary care hospital in Saitama, Japan, and assessed the characteristic of the strains using a whole genome sequencing (WGS)-based approach. METHODS: CA-MRSA strains isolated from infected patients who required hospitalization for treatment were evaluated in this study. Antimicrobial susceptibility tests, molecular typing by PCR and pulse-field gel electrophoresis (PFGE) were performed to characterize MRSA strains. WGS was performed for detailed genetic analysis. RESULTS: A total of 582 MRSA strains (35.2%) were identified among 1625 S. aureus strains collected during the study period. Ten MRSA strains (1.7%) were defined as CA-MRSA clinically, and all were isolated from pediatric patients. All strains mainly caused purulent lymphadenitis, were susceptible to fluoroquinolone and tetracycline, exhibited sequence type (ST) 834 or its single-locus variants and contained staphylococcal cassette chromosome mec (SCCmec) type IVc. Phylogenic analysis by PFGE and WGS revealed close relatedness of all strains, with the number of single nucleotide polymorphisms ranging from 35 to 119 by WGS. Out of the ten strains, nine possessed the genomic island SaPISaitama2 containing tst, sec and sel genes. SaPISaitama2 comprises a mosaic of genomic islands SaPIm4 and SaPIm1 harbored by a hospital-associated MRSA strain Mu50. CONCLUSIONS: This study describes a regional outbreak of ST834-related CA-MRSA in children with a unique pathogenicity island in Japan. Pediatric patient tropism of this clone could be enhanced by susceptibility to fluoroquinolones and tetracyclines, which cannot be prescribed to children.

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  • Fecal Freezing Preservation Period Influences Colonization Ability for Fecal Microbiota Transplantation. Reviewed

    Takahashi M, Ishikawa D, Sasaki T, Lu YJ, Kuwahara-Arai K, Kamei M, Shibuya T, Osada T, Hiramatsu K, Nagahara A

    J Appl Microbiol.   126 ( 3 )   973 - 984   2019

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  • The Microbial Composition of Bacteroidetes Species in Ulcerative Colitis Is Effectively Improved by Combination Therapy With Fecal Microbiota Transplantation and Antibiotics. Reviewed International journal

    Dai Ishikawa, Takashi Sasaki, Masahito Takahashi, Kyoko Kuwahara-Arai, Keiichi Haga, Shoko Ito, Koki Okahara, Akihito Nakajima, Tomoyoshi Shibuya, Taro Osada, Keiichi Hiramatsu, Sumio Watanabe, Akihito Nagahara

    Inflammatory bowel diseases   24 ( 12 )   2590 - 2598   2018.11

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    Background: We previously reported that fresh fecal microbiota transplantation (FMT) after triple-antibiotic therapy (amoxicillin, fosfomycin, and metronidazole [AFM]; A-FMT) synergistically contributed to the recovery of phylum Bacteroidetes composition associated with the endoscopic severity and treatment efficacy of ulcerative colitis (UC). Here, we performed further microbial analyses using a higher-resolution method to identify the key bacterial species in UC and determine whether viable Bacteroidetes species from donor feces were successfully colonized by A-FMT. Methods: The taxonomic composition of Bacteroidetes in 25 healthy donors and 27 UC patients at baseline was compared at the species level using a heat-shock protein (hsp) 60-based microbiome method. Microbiota alterations before and after treatment of UC patients were also analyzed in 24 cases (n = 17 A-FMT; n = 3 mono-AFM; n = 4 mono-FMT). Results: We found species-level dysbiosis within the phylum Bacteroidetes in UC samples, which was associated with reduced species diversity, resulting from hyperproliferation and hypoproliferation of particular species. Moreover, in responders treated with A-FMT, diversity was significantly recovered at 4 weeks after a fresh round of FMT, after which high degrees of similarity in Bacteroidetes species composition among recipients and donors were observed. Conclusions: A-FMT alleviated intestinal dysbiosis, which is caused by the loss of Bacteroidetes species diversity in patients with UC. Eradication of dysbiotic indigenous Bacteroidetes species by AFM pretreatment might promote the colonization of viable Bacteroidetes cells, thereby improving the intestinal microbiota dysbiosis induced by UC. Our findings serve as a basis for further investigations into the mechanisms of FMT.

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  • Development of a New Application for Comprehensive Viability Analysis Based on Microbiome Analysis by Next-Generation Sequencing: Insights into Staphylococcal Carriage in Human Nasal Cavities. Reviewed International journal

    Yu Jie Lu, Takashi Sasaki, Kyoko Kuwahara-Arai, Yuki Uehara, Keiichi Hiramatsu

    Applied and environmental microbiology   84 ( 11 )   e00517 - 18   2018.6

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    The nasal carriage rate of Staphylococcus aureus in human is 25 to 30%, and S. aureus sporadically causes severe infections. However, the mechanisms underlying staphylococcal carriage remain largely unknown. In the present study, we constructed an rpoB-based microbiome method for staphylococcal species discrimination. Based on a microbiome scheme targeting viable cell DNA using propidium monoazide (PMA) dye (PMA microbiome method), we also developed a new method to allow the comprehensive viability analysis of any bacterial taxon. To clarify the ecological distribution of staphylococci in the nasal microbiota, we applied these methods in 46 nasal specimens from healthy adults. PMA microbiome results showed that Staphylococcaceae and Corynebacteriaceae were the most predominant viable taxa (average relative abundance: 0.435262 and 0.375195, respectively), and Staphylococcus epidermidis exhibited the highest viability in the nasal microbiota. Staphylococcus aureus detection rates from nasal specimens by rpoB-based conventional and PMA microbiome methods were 84.8% (39 of 46) and 69.5% (32 of 46), respectively, which substantially exceeded the values obtained by a culture method using identical specimens (36.9%). Our results suggest that Staphylococcaceae species, especially S. epidermidis, adapted most successfully to human nasal cavity. High detection of S. aureus DNA by microbiome methods suggests that almost all healthy adults are consistently exposed to S. aureus in everyday life. Furthermore, the large difference in S. aureus detection rates between culture and microbiome methods suggests that S. aureus cells frequently exist in a viable but nonculturable state in nasal cavities. Our method and findings will contribute to a better understanding of the mechanisms underlying carriage of indigenous bacteria.IMPORTANCE Metagenomic analyses, such as 16S rRNA microbiome methods, have provided new insights in various research fields. However, conventional 16S rRNA microbiome methods do not permit taxonomic analysis of only the viable bacteria in a sample and have poor resolving power below the genus level. Our new schemes allowed for viable cell-specific analysis and species discrimination, and nasal microbiome data using these methods provided some interesting findings regarding staphylococcal nasal carriage. According to our comprehensive viability analysis, the high viability of Staphylococcus species, especially Staphylococcus epidermidis, in human nasal carriage suggests that this taxon has adapted most successfully to human nasal tissue. Also, a higher detection rate of S. aureus DNA by microbiome methods (84.8%) than by a culture method (36.9%) suggests that almost all healthy adults are consistently exposed to Staphylococcus aureus in the medium and long term. Our findings will contribute to a better understanding of the mechanisms underlying the carriage of indigenous bacteria.

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  • Risk factors of fecal colonization with extended-spectrum β-lactamase-producing Enterobacteriaceae in special nursing homes in Japan. Reviewed

    Kumi Yokoyama, Yuki Uehara, Takashi Sasaki, Keiichi Hiramatsu

    Journal of general and family medicine   19 ( 3 )   90 - 96   2018.5

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    Objective: Japanese welfare facilities for the elderly are called as special nursing home (SNH), providing conventional-type with group care or unit-type with individual care. We investigated the risk factors of fecal colonization with extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBL-E) of elderly who required care at SNH in Japan. Methods: The feces discharged on diaper were obtained from the total of 100 residents with fecal incontinence in 9 SNHs located in Tokyo, Japan. The samples were cultured on ESBL selection agar, and ESBL-E were determined by the antimicrobial susceptibility test and genetic analysis. The status of the residents and the characteristics of facilities, especially about the incontinence care, were obtained by questionnaire methods. Statistical analysis was performed to determine the factors related to carriage of ESBL-E. Results: Extended-spectrum β-lactamase-producing Enterobacteriaceae was isolated from 53 of 100 SNH residents. Risk factors of colonization among the individual residents were not found. The prevalence of ESBL-E carriage was significantly higher in the 6 conventional-type facilities than in the 3 unit-type facilities (P = .015). The cart for diaper exchange was used in 5 of 6 conventional-type facilities in 9 SNHs, and their residents tended to show high of ESBL-E colonization rate. The residents living in unit-type facilities which do not use gloves for changing diaper tended to show high ESBL-E colonization rate than other 2 facilities using gloves. Conclusions: It is suggested that using the cart for changing diaper has relation to carry ESBL-E. In the facilities using cart, revision of their methods of excretion care will be needed.

    DOI: 10.1002/jgf2.161

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  • Maternal High Fiber Diet during Pregnancy and Lactation Influences Regulatory T Cell Differentiation in Offspring in Mice Reviewed

    Akihito Nakajima, Naoko Kaga, Yumiko Nakanishi, Hiroshi Ohno, Junki Miyamoto, Ikuo Kimura, Shohei Hori, Takashi Sasaki, Keiichi Hiramatsu, Ko Okumura, Sachiko Miyake, Sonoko Habu, Sumio Watanabe

    JOURNAL OF IMMUNOLOGY   199 ( 10 )   3516 - 3524   2017.11

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    DOI: 10.4049/jimmunol.1700248

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  • In Vitro Tolerance of Drug-Naive Staphylococcus aureus Strain FDA209P to Vancomycin Reviewed

    Madhuri Singh, Miki Matsuo, Takashi Sasaki, Yuh Morimoto, Tomomi Hishinuma, Keiichi Hiramatsu

    ANTIMICROBIAL AGENTS AND CHEMOTHERAPY   61 ( 2 )   e01154 - 16   2017.2

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    DOI: 10.1128/AAC.01154-16

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  • Activity of tick antimicrobial peptide from Ixodes persulcatus (persulcatusin) against cell membranes of drug-resistant Staphylococcus aureus Reviewed

    Naruhide Miyoshi, Emiko Isogai, Keiichi Hiramatsu, Takashi Sasaki

    JOURNAL OF ANTIBIOTICS   70 ( 2 )   142 - 146   2017.2

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    DOI: 10.1038/ja.2016.101

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  • Feline coronavirus replication is affected by both cyclophilin A and cyclophilin B Reviewed

    Yoshikazu Tanaka, Yuka Sato, Takashi Sasaki

    JOURNAL OF GENERAL VIROLOGY   98 ( 2 )   190 - 200   2017.2

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    DOI: 10.1099/jgv.0.000663

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  • Changes in Intestinal Microbiota Following Combination Therapy with Fecal Microbial Transplantation and Antibiotics for Ulcerative Colitis Reviewed

    Dai Ishikawa, Takashi Sasaki, Taro Osada, Kyoko Kuwahara-Arai, Keiichi Haga, Tomoyoshi Shibuya, Keiichi Hiramatsu, Sumio Watanabe

    INFLAMMATORY BOWEL DISEASES   23 ( 1 )   116 - 125   2017.1

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    DOI: 10.1097/MIB.0000000000000975

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  • バンコマイシン投与中にMIC上昇を認めたMRSA臨床分離株の遺伝子変異

    森 美紀, 上原 由紀, 平松 啓一, 菊池 賢, 佐々木 崇

    日本化学療法学会雑誌   64 ( Suppl.A )   182 - 182   2016.5

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  • Complete genome sequence of vancomycin-intermediate Staphylococcus aureus strain MI (HIP5827) Reviewed International journal

    Tomomi Hishinuma, Yuki Katayama, Miki Matsuo, Takashi Sasaki, Keiichi Hiramatsu

    Genome Announcements   4 ( 2 )   e00123 - 16   2016

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    DOI: 10.1128/genomeA.00123-16

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  • Apigenin as an anti-quinolone-resistance antibiotic Reviewed

    Yuh Morimoto, Tadashi Baba, Takashi Sasaki, Keiichi Hiramatsu

    INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS   46 ( 6 )   666 - 673   2015.12

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    DOI: 10.1016/j.ijantimicag.2015.09.006

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  • Molecular epidemiological study of feline coronavirus strains in Japan using RT-PCR targeting nsp14 gene Reviewed

    Yoshikazu Tanaka, Takashi Sasaki, Ryo Matsuda, Yosuke Uematsu, Tomohiro Yamaguchi

    BMC VETERINARY RESEARCH   11 ( 57 )   2015.3

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    DOI: 10.1186/s12917-015-0372-2

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  • Cellular peptidyl-prolyl cis/trans isomerase Pin1 facilitates replication of feline coronavirus. Reviewed

    Tanaka Y, Amano A, Morisaki M, Sato Y, Sasaki T

    Antiviral Res.   7 ( 126 )   1 - 7   2015

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  • Future Chemotherapy Preventing Emergence of Multi-Antibiotic Resistance. Reviewed

    Hiramatsu K, Sasaki T, Morimoto Y

    Juntendo Medical Journal.   3 ( 3 )   249 - 256   2015

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    The authors and all of the faculty at the Department of Bacteriology (Dept. of Microbiology from April 2015) have studied methicillin-resistant Staphylococcus aureus (MRSA), a representative multi-drug-resistant pathogen prevalent globally. During this study, we have identified the extreme flexibility of this organism to survive antibiotic pressure. S. aureus is part of the normal flora of human beings, yet it possesses high pathogenic potential, being aptly called 'the department of toxins'. We are probably destined to continue our lives in association with this dangerous neighbor. For this reason, in 2008, KH launched a new project searching for novel antibiotics that are effective against MRSA. A newly found antibiotic called nybomycin has a curious property: it is effective against quinolone-resistant S. aureus strains (including most MRSA), but not against quinolone-susceptible ones. Moreover, the mutant strains derived from the parent S. aureus strain after treatment with nybomycin were cured of their quinolone resistance. Subsequently, we found an antibiotic with the same property in flavones, too. We designated these antibiotics with such unique properties reverse antibiotics (RA). By using RA and extant antibiotics in a well-controlled way, we should be able to establish sophisticated anti-microbial chemotherapy in the future.

    DOI: 10.14789/jmj.61.249

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  • Complete genome sequence of methicillin-resistant Staphylococcus schleiferi strain TSCC54 of canine origin Reviewed

    Takashi Sasaki, Sae Tsubakishita, Kyoko Kuwahara-Arai, Miki Matsuo, Yu Jie Lu, Yoshikazu Tanaka, Keiichi Hiramatsu

    Genome Announcements   3 ( 5 )   e01268 - 15   2015

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    DOI: 10.1128/genomeA.01268-15

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  • Complete Genome Sequence of a Drug-naive Classical Staphylococcus aureus Strain FDA209P. Reviewed International journal

    Singh M, Sasaki T, Matsuo M, Morimoto Y, Aiba Y, Hiramatsu K

    Genome Announc.   12 ( 3(6) )   e01343 - 15   2015

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    We report the complete genome sequence of the methicillin-sensitive Staphylococcus aureus (MSSA) strain FDA209P (ATCC 6538P and NCTC 7447).

    DOI: 10.1128/genomeA.01343-15

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  • Treatment of a case of feline infectious peritonitis with cyclosporin A. Reviewed

    Tanaka Y, Sato Y, Takahashi D, Matsumoto H, Sasaki T

    Vet Rec Case Rep.   3   e000134   2015

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  • Multi-drug-resistant Staphylococcus aureus and future chemotherapy Reviewed

    K. Hiramatsu, Y. Katayama, M. Matsuo, T. Sasaki, Y. Morimoto, A. Sekiguchi, T. Baba

    JOURNAL OF INFECTION AND CHEMOTHERAPY   20 ( 9-10 )   593 - 601   2014.9

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    DOI: 10.1016/j.jiac.2014.08.001

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  • Suppression of Coronavirus Replication by Cyclophilin Inhibitors Reviewed

    Yoshikazu Tanaka, Yuka Sato, Takashi Sasaki

    VIRUSES-BASEL   5 ( 5 )   1250 - 1260   2013.5

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    DOI: 10.3390/v5051250

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  • Genomic basis for methicillin resistance in Staphylococcus aureus Reviewed

    Keiichi Hiramatsu, Teruyo Ito, Sae Tsubakishita, Takashi Sasaki, Fumihiko Takeuchi, Yuh Morimoto, Yuki Katayama, Miki Matsuo, Kyoko Kuwahara-Arai, Tomomi Hishinuma, Tadashi Baba

    Infection and Chemotherapy   45 ( 2 )   117 - 136   2013

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    DOI: 10.3947/ic.2013.45.2.117

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  • Characterization of Staphylococcus aureus isolates from faecal samples of the Straw-Coloured Fruit Bat (Eidolon helvum) in Obafemi Awolowo University (OAU), Nigeria Reviewed

    Babatunji Akobi, Oladipo Aboderin, Takashi Sasaki, Adebayo Shittu

    BMC MICROBIOLOGY   12 ( 12(1) )   279   2012.11

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    DOI: 10.1186/1471-2180-12-279

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  • Population Genetic Structures of Staphylococcus aureus Isolates from Cats and Dogs in Japan Reviewed

    Takashi Sasaki, Sae Tsubakishita, Yoshikazu Tanaka, Masayuki Ohtsuka, Isamu Hongo, Tsuneo Fukata, Hidenori Kabeya, Soichi Maruyama, Keiichi Hiramatsu

    JOURNAL OF CLINICAL MICROBIOLOGY   50 ( 6 )   2152 - 2155   2012.6

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    DOI: 10.1128/JCM.06739-11

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  • Suppression of feline coronavirus replication in vitro by cyclosporin A Reviewed

    Yoshikazu Tanaka, Yuka Sato, Shuichi Osawa, Mai Inoue, Satoka Tanaka, Takashi Sasaki

    VETERINARY RESEARCH   43 ( 43(1) )   41   2012.4

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    DOI: 10.1186/1297-9716-43-41

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  • Rapid and Accurate Identification of Human-Associated Staphylococci by Use of Multiplex PCR Reviewed

    Shintaro Hirotaki, Takashi Sasaki, Kyoko Kuwahara-Arai, Keiichi Hiramatsu

    JOURNAL OF CLINICAL MICROBIOLOGY   49 ( 10 )   3627 - 3631   2011.10

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    DOI: 10.1128/JCM.00488-11

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  • Origin and molecular evolution of the determinant of methicillin resistance in staphylococci (Antimicrobial Agents and Chemotherapy (2010) 54, 10 (4352?4359)) Reviewed

    Sae Tsubakishita, Kyoko Kuwahara-Arai, Takashi Sasaki, Keiichi Hiramatsu

    Antimicrobial Agents and Chemotherapy   55 ( 2 )   946   2011.2

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    DOI: 10.1128/AAC.01663-10

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  • 健康な犬におけるメチシリン耐性Staphylococcus pseudintermedius(MRSP)の疫学調査 Reviewed

    須藤哲長, 寺井陽子, 三枝早苗, 椿下早絵, 佐々木崇, 平松啓一

    獣医臨床皮膚科   17 ( 2 )   79 - 83   2011

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    In veterinary medicine, the use of broad-spectrum antibiotics has been increasing. The prevalence of methicillin-resistant <i>Staphylococcus pseudintermedius</i> (MRSP) in dogs is now increasingly common all over the world, and has also become a serious issue in veterinary dermatology practice in Japan. In the present study, we surveyed nasal carriage of MRSP and methicillin-resistant <i>S. aureus</i> (MRSA) in 104 healthy dogs in Japan, and compared the results with those of 102 patient dogs under secondary veterinary medical care. Nasal carriage rates of MRSP in healthy and patient dogs were 4.8% and 21.6%, respectively, and that of patient dogs was a significantly higher value (p<0.001), suggesting that patient dogs under secondary veterinary medical care were under antibiotic selective pressure. The MRSP carriage rate in healthy dogs in Japan was similar to those reported overseas. MRSA nasal carriage rates in healthy and patient dogs were 0% and 1.96%, respectively, with no significant difference between the two (p=0.244). Under antibiotic selective pressures, MRSA carriage rate in dogs didn’t increase significantly, suggesting that dogs have low potential as a reservoir of MRSA.<br>

    DOI: 10.2736/jjvd.17.79

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  • Origin and Molecular Evolution of the Determinant of Methicillin Resistance in Staphylococci Reviewed

    Sae Tsubakishita, Kyoko Kuwahara-Arai, Takashi Sasaki, Keiichi Hiramatsu

    ANTIMICROBIAL AGENTS AND CHEMOTHERAPY   54 ( 10 )   4352 - 4359   2010.10

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    DOI: 10.1128/AAC.00356-10

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  • Multiplex-PCR Method for Species Identification of Coagulase-Positive Staphylococci Reviewed

    Takashi Sasaki, Sae Tsubakishita, Yoshikazu Tanaka, Arihito Sakusabe, Masayuki Ohtsuka, Shintaro Hirotaki, Tetsuji Kawakami, Tsuneo Fukata, Keiichi Hiramatsu

    JOURNAL OF CLINICAL MICROBIOLOGY   48 ( 3 )   765 - 769   2010.3

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    DOI: 10.1128/JCM.01232-09

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  • Reclassification of Canine Staphylococcal Strains Identified as Methicillin-resistant Staphylococcus aureus (MRSA) in a Clinical Laboratory Reviewed

    Kasai Tomoko, Saegusa Sanae, Sasaki Takashi

    The Japanese Journal of Veterinary Dermatology   16 ( 3 )   119 - 124   2010

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    DOI: 10.2736/jjvd.16.119

    DOI: 10.2736/jjvd.17.99_references_DOI_ZXvPUDGSDlyIuIaMb7t0T183VBZ

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  • Emergence of Quinolone-Resistant Bordetella pertussis in Japan Reviewed

    Masayuki Ohtsuka, Ken Kikuchi, Kenichiro Shimizu, Namiko Takahashi, Yuka Ono, Takashi Sasaki, Keiichi Hiramatsu

    ANTIMICROBIAL AGENTS AND CHEMOTHERAPY   53 ( 7 )   3147 - 3149   2009.7

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    DOI: 10.1128/AAC.00023-09

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  • Genetic Diversity of Staphylocoagulase Genes (coa): Insight into the Evolution of Variable Chromosomal Virulence Factors in Staphylococcus aureus Reviewed

    Shinya Watanabe, Teruyo Ito, Takashi Sasaki, Shanshuang Li, Ikuo Uchiyama, Kozue Kishii, Ken Kikuchi, Robert Leo Skov, Keiichi Hiramatsu

    PLOS ONE   4 ( 5 )   e5714   2009.5

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    DOI: 10.1371/journal.pone.0005714

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  • Smqnr, a new chromosome-carried quinolone resistance gene in Stenotrophomonas maltophilia Reviewed

    Kenichiro Shimizu, Ken Kikuchi, Takashi Sasaki, Namiko Takahashi, Masayuki Ohtsuka, Yuka Ono, Keiichi Hiramatsu

    ANTIMICROBIAL AGENTS AND CHEMOTHERAPY   52 ( 10 )   3823 - 3825   2008.10

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    DOI: 10.1128/AAC.00026-08

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  • 多剤耐性緑膿菌に対するaztreonamとarbekacinによる併用療法

    菊池 賢, 星 最智, 佐々木 崇, 堀 賢, 平松 啓一

    感染症学雑誌   82 ( 5 )   567 - 567   2008.9

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  • Is Histoplasma capsulatum a native inhabitant of Japan ? Reviewed

    Ken Kikuchi, Takashi Sugita, Koichi Makimura, Kensaku Urata, Takashi Someya, Takashi Sasaki, Katsuhiko Kamei, Masakazu Niimi, Keiichi Hiramatsu, Yoshimasa Uehara

    MICROBIOLOGY AND IMMUNOLOGY   52 ( 9 )   455 - 459   2008.9

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    DOI: 10.1111/j.1348-0421.2008.00052.x

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  • Postantibiotic effects and bactericidal activities of Levofloxacin and gatifloxacin at concentrations simulating those of topical ophthalmic administration against fluoroquinolone-resistant, and fluoroquinolone-sensitive methicillin-resistant staphylococcus aureus strains Reviewed

    Saichi Hoshi, Ken Kikuchi, Takashi Sasaki, Chie Sotozono, Shigeru Kinoshita, Keiichi Hiramatsu

    ANTIMICROBIAL AGENTS AND CHEMOTHERAPY   52 ( 8 )   2970 - 2973   2008.8

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    DOI: 10.1128/AAC.01466-07

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  • 多剤耐性緑膿菌に対するaztreonamとarbekacinによる併用療法

    菊池 賢, 星 最智, 佐々木 崇, 堀 賢, 平松 啓一

    感染症学雑誌   82 ( 臨増 )   248 - 248   2008.3

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  • Reclassification of phenotypically identified Staphylococcus intermedius strains Reviewed

    Takashi Sasaki, Ken Kikuchi, Yoshikazu Tanaka, Namiko Takahashi, Shinichi Kamata, Keiichi Hiramatsu

    JOURNAL OF CLINICAL MICROBIOLOGY   45 ( 9 )   2770 - 2778   2007.9

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    DOI: 10.1128/JCM.00360-07

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  • Methicillin-resistant Staphylococcus pseudintermedius in a veterinary teaching hospital Reviewed

    Takashi Sasaki, Ken Kikuchi, Yoshikazu Tanaka, Namiko Takahashi, Shinichi Kamata, Keiichi Hiramatsu

    JOURNAL OF CLINICAL MICROBIOLOGY   45 ( 4 )   1118 - 1125   2007.4

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    DOI: 10.1128/JCM.02193-06

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  • イヌの膿皮症治療薬と薬剤耐性菌の歴史的変遷

    佐々木崇( Role: Contributor)

    第20回日本獣医皮膚科学会学術大会記念誌  2017.3 

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  • 人獣共通感染症

    佐々木崇( Role: Contributorブドウ球菌感染症)

    医薬ジャーナル社  2016.2 

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  • 感染症診断における細胞診と細菌検査

    佐々木崇( Role: Contributor)

    Small Animal Dermatology  2014.9 

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  • 小動物臨床におけるブドウ球菌同定の実際

    佐々木崇( Role: Contributor)

    MVM (Journal of Modern Veterinary Medicine)  2009.11 

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MISC

  • 犬の表在性膿皮症におけるクロルヘキシジン外用療法とセファレキシン全身療法の治療効果比較

    佐々木崇, 山崎真大, 原田和記, 伊従慶太, 山岸建太郎, 永田雅彦, 西藤公司, 加納塁

    日本獣医皮膚科学会学術大会・総会   27th   2024

  • Molecular epidemiology of methicillin-resistant Staphylococcus pseudintermedius in canine pyoderma

    佐々木崇, 山崎真大, 原田和記, 西藤公司

    日本細菌学雑誌(Web)   79 ( 2 )   2024

  • 図解 日本獣医皮膚科学会推進研究の紹介 イヌ表在性膿皮症の一次診療症例に対するクロルヘキシジン外用療法およびセファレキシン全身療法の治療効果比較

    佐々木 崇

    獣医臨床皮膚科   29 ( 2 )   87 - 95   2023.6

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    Language:Japanese   Publisher:(一社)日本獣医皮膚科学会  

    Ichushi

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  • 図解 日本獣医皮膚科学会推進研究の紹介 イヌ表在性膿皮症一次診療症例の薬剤耐性動向

    佐々木 崇

    獣医臨床皮膚科   29 ( 1 )   17 - 25   2023.3

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    Language:Japanese   Publisher:(一社)日本獣医皮膚科学会  

    Ichushi

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  • イヌの表在性膿皮症におけるクロルヘキシジン外用治療法およびセファレキシン全身療法の治療効果比較~2022年の研究成果と今後の目標~

    山崎真大, 佐々木崇, 原田和記, 伊從慶太, 山岸建太郎, 西藤公司, 永田雅彦

    日本獣医皮膚科学会学術大会・総会   26th   2023

  • イヌの表在性膿皮症におけるクロルヘキシジン外用治療法およびセファレキシン全身療法の治療効果比較~2021年の研究成果と今後の目標~

    山崎真大, 佐々木崇, 原田和記, 伊從慶太, 山岸建太郎, 西藤公司, 永田雅彦

    日本獣医皮膚科学会学術大会・総会   25th   2022

  • イヌの表在性膿皮症におけるクロルヘキシジン外用治療法およびセファレキシン全身療法の治療効果比較~これまでの研究成果と今後の目標~

    山崎真大, 佐々木崇, 原田和記, 伊從慶太, 山岸建太郎, 西藤公司, 永田雅彦

    日本獣医皮膚科学会学術大会・総会   24th   2021

  • 本邦のHIV患者におけるUSA300株MRSAの流行

    池内 和彦, 安達 英輔, 佐々木 崇, 鈴木 正人, 林 阿英, 齋藤 真, 古賀 道子, 堤 武也, 城戸 康年, 上原 由紀, 四柳 宏

    日本エイズ学会誌   22 ( 4 )   443 - 443   2020.11

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    Language:Japanese   Publisher:(一社)日本エイズ学会  

    Ichushi

    J-GLOBAL

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  • Fecal Freeze Storage Period Influences Colonization Ability for Fecal Microbiota Transplantation

    佐々木崇, 佐々木崇, 石川大, 高橋正倫, LU Yu Jie, 桑原京子, 平松啓一

    日本細菌学雑誌(Web)   74 ( 1 )   2019

  • 生細菌特異的な健常人鼻腔内細菌叢解析

    呂 宇杰, 佐々木 崇, 桑原 京子, 上原 由紀, 平松 啓一

    日本細菌学雑誌   73 ( 1 )   77 - 77   2018.2

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    Ichushi

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  • MRSA選択分離培地の評価

    駒田薫, 駒田薫, 大塚正之, 佐々木崇, 須田友理, 須田友理, 菱沼俊樹, 菱沼俊樹, 金桝聖, 金桝聖

    神奈川県臨床検査技師会雑誌   52   2018

  • Canine Superficial Pyoderma: an Indication for Antimicrobial and Topical Therapies

    山崎真大, 加納塁, 原田和記, 村山信雄, 佐々木崇, 折戸謙介, 近藤広孝, 村井妙, 山岸建太郎, 西藤公司, 永田雅彦, 永田雅彦

    獣医臨床皮膚科   23 ( 3 )   127 - 134   2017.9

  • 【視野を広げる皮膚科診療のTips(秘訣)第10回 皮膚科の"お悩み"相談室】膿皮症 膿皮症でメチシリン耐性ブドウ球菌・多剤耐性ブドウ球菌が検出されたときの対処方法を教えてください

    佐々木 崇

    Small Animal Dermatology   13 ( 4 )   27 - 28   2017.7

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    Language:Japanese   Publisher:(株)エデュワードプレス  

    Ichushi

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  • 復帰抗生物質は細菌の種分化に関与したか?

    馬場 理, 杉山 遥夏, 佐々木 崇, 森本 ゆふ, 平松 啓一

    日本細菌学雑誌   72 ( 1 )   170 - 170   2017.2

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    Language:Japanese   Publisher:日本細菌学会  

    Ichushi

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  • 鼻腔・口腔常在菌のキノロン耐性/感受性について

    杉山 遥夏, 馬場 理, 佐々木 崇, 平松 啓一

    日本細菌学雑誌   72 ( 1 )   169 - 169   2017.2

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    Ichushi

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  • 薬剤耐性菌に対する抗菌ペプチドPersulcatusinの効果とその抗菌メカニズム

    両角 一輝, 佐々木 崇, 平松 啓一, 小林 宣道, 菊池 賢, 磯貝 恵美子

    日本細菌学雑誌   72 ( 1 )   135 - 135   2017.2

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    Ichushi

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  • 実験動物マウスと健常人におけるBacteroidales腸内細菌叢比較

    佐々木 崇, 桑原 京子, 呂 宇傑, 石川 大, 中島 章人, 平松 啓一

    日本細菌学雑誌   72 ( 1 )   57 - 57   2017.2

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    Ichushi

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  • 実験動物マウスと健常人におけるBacteroidales腸内細菌叢比較

    佐々木崇, 桑原京子, LU Jie Yu, 石川大, 中島章人, 平松啓一

    日本細菌学雑誌(Web)   72 ( 1 )   2017

  • Molecular mechanism of vancomycin tolerance in Staphylococcus aureus is analogous to stringent transcriptional pattern: detected by RNA sequencing

    SINGH Madhuri, MATSUO Miki, SASAKI Takashi, HISHINUMA Tomomi, HIRAMATSU Keiichi

    日本生化学会大会(Web)   90th   2017

  • The mechanism of vancomycin resistance in VISA and the role of reverse antibiotic (RA)

    Keiichi Hiramatsu, Yuhu Morimoto, Tadashi Baba, Takashi Sasaki, Tomomi Hishinuma, Yuki Katayama, Miki Matsuo, Kyoko Kuwahara, Yuki Uehara, Masayuki Igarashi

    Japanese Journal of Chemotherapy   64 ( 3 )   503 - 512   2016.5

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    Language:Japanese   Publishing type:Book review, literature introduction, etc.   Publisher:Japan Society of Chemotherapy  

    J-GLOBAL

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  • 難治性MRSA感染症の再燃に関与しているslow-VISA(バンコマイシン中間耐性黄色ブドウ球菌)について

    片山 由紀, 菱沼 知美, 松尾 美記, 相羽 由詞, 平松 啓一, 佐々木 崇, 関根 美和

    日本化学療法学会雑誌   64 ( 3 )   591 - 591   2016.5

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    Ichushi

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  • バンコマイシン中間耐性MRSA(VISA)の耐性機構と復帰抗生物質

    平松 啓一, 森本 ゆふ, 馬場 理, 佐々木 崇, 菱沼 知美, 片山 由紀, 松尾 美記, 桑原 京子, 上原 由紀, 五十嵐 雅之

    日本化学療法学会雑誌   64 ( 3 )   503 - 512   2016.5

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    Ichushi

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  • 黄色ブドウ球菌のキノロン系薬トレランス株の解析

    平松 未悠, 菱沼 知美, 森本 ゆふ, 平松 啓一, 佐々木 崇

    日本化学療法学会雑誌   64 ( Suppl.A )   182 - 182   2016.5

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    Ichushi

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  • 次世代シーケンサーを用いたブドウ球菌属特異的細菌叢解析法の構築

    Lu Yujie, 佐々木 崇, 桑原 京子, 平松 啓一

    日本細菌学雑誌   71 ( 1 )   61 - 61   2016.2

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    Language:Japanese   Publisher:日本細菌学会  

    Ichushi

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  • 環境中のキノロン耐性菌について

    馬場 理, 佐々木 崇, 森本 ゆふ, 平松 啓一

    日本細菌学雑誌   71 ( 1 )   113 - 113   2016.2

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    Ichushi

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  • CRISPR領域の配列解析によるSCCmec V型の進化学的伝播経路の推定

    佐々木 崇, 呂 宇傑, 平松 啓一

    日本細菌学雑誌   71 ( 1 )   135 - 135   2016.2

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    Language:Japanese   Publisher:日本細菌学会  

    Ichushi

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  • Staphylococcus aureusにおいてバンコマイシン抵抗性を持つslow VISA表現型の特徴(Characterization of slow VISA Phenotype of Vancomycin Resistance in Staphylococcus aureus)

    片山 由紀, 菱沼 知美, 岩本 昭, 相羽 由詞, 佐々木 崇, 松尾 美記, 平松 啓一

    日本化学療法学会雑誌   63 ( Suppl.A )   171 - 171   2015.5

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    Ichushi

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  • 市中発生のMRSAによるブドウ球菌性熱傷様皮膚症候群の分子疫学的検討

    上原 由紀, 廣瀧 慎太郎, 堀越 裕歩, 平松 啓一, 佐々木 崇, 飯坂 健太, 神保 泰之

    感染症学雑誌   89 ( 臨増 )   192 - 192   2015.3

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    Ichushi

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  • 黄色ブドウ球菌のrpoB変異による種々の薬剤感受性への影響

    相羽 由詞, 片山 由紀, 菱沼 知美, 佐々木 崇, 桑原 京子, 平松 啓一

    日本細菌学雑誌   70 ( 1 )   195 - 195   2015.2

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    Ichushi

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  • 新規バンコマイシン耐性の表現型であるslow-VISAの耐性化機構について(Characterization of slow VISA , A Novel Phenotype of Vancomycin Resistance in Staphylococcus aureus)

    片山 由紀, 菱沼 知美, 岩本 昭, 相羽 由詞, 佐々木 崇, 松尾 美記, 平松 啓一

    日本細菌学雑誌   70 ( 1 )   194 - 194   2015.2

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    Ichushi

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  • 伴侶動物におけるブドウ球菌感染症の実態

    佐々木崇

    日本ブドウ球菌研究会プログラム・講演要旨集   59th   2014

  • クマ科を自然宿主とするブドウ球菌Staphylococcus schleiferiの生態とゲノム進化

    佐々木崇, 椿下早絵, 植田美弥, 片山敦司, 山崎晃司, 葛西真輔, 鳥居春己, 平松啓一

    日本獣医学会学術集会講演要旨集   155th   2013

  • ORIGIN AND MOLECULAR EVOLUTION OF THE DETERMINANT OF METHICILLIN RESISTANCE IN STAPHYLOCOCCI

    TSUBAKISHITA Sae, KUWAHARA-ARAI Kyoko, SASAKI Takashi, HIRAMATSU Keiichi

    日本細菌学雑誌   66 ( 2-3 )   2011

  • Molecular Evolution of MRSA 2010

    K. Hiramatsu, S. Tsubakishita, M. Matsuo, T. Sasaki

    12TH WESTERN PACIFIC CONGRESS ON CHEMOTHERAPY AND INFECTIOUS DISEASES   11 - 17   2011

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    Language:English   Publishing type:Article, review, commentary, editorial, etc. (international conference proceedings)  

    Web of Science

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  • Systemic administration of Linezolid for Postoperative Endophthalmitis

    HOSHI Saichi, HASHIDA Masatsugu, SASAKI Takashi

    23 ( 4 )   625 - 628   2010.10

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    Language:Japanese  

    CiNii Research

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  • 哺乳類宿主におけるブドウ球菌の進化生態学的研究

    佐々木崇, 椿下早絵, 柿澤恵子, 吉羽宣明, 深田恒夫, 伊藤豊志雄, 井上貴史, 江袋進, 佐藤梓, 池辺祐介, 平松啓一

    日本獣医学会学術集会講演要旨集   150th   2010

  • 検査機関でMRSAと同定された犬由来ブドウ球菌株の分類学的再検討

    浅野(笠井)智子, 三枝早苗, 佐々木崇

    日本獣医皮膚科学会学術大会・総会   13th   2010

  • 黄色ブドウ球菌クローンの宿主特異的な進化とポピュレーション構造:様々な動物種における生態学的評価

    佐々木崇, 椿下早絵, 大澤弘宜, 大澤弘宜, 岩本昭, 広瀧慎太郎, 壁谷英則, 名和徹, 丸山総一, 平松啓一, 平松啓一

    日本細菌学雑誌   65 ( 1 )   2010

  • メチシリン耐性遺伝子の起源と分子進化

    椿下早絵, 桑原京子, 桑原京子, 佐々木崇, 平松啓一, 平松啓一

    日本ブドウ球菌研究会プログラム・講演要旨集   55th   2010

  • 我が国の血流感染分離Candida主要4菌種の遺伝的多様性

    菊池 賢, 佐々木 崇, 上原 由紀, 大串 大輔, 廣瀧 慎太郎, 清水 健一郎, 大塚 正之, 小野 由可, 野竹 重幸, 平松 啓一

    日本細菌学雑誌   64 ( 1 )   170 - 170   2009.2

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    Language:Japanese   Publisher:日本細菌学会  

    Ichushi

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  • 小動物臨床におけるブドウ球菌同定の実際

    佐々木崇

    MVM   18 ( 7 )   2009

  • 小動物皮膚科領域におけるメチシリン耐性ブドウ球菌感染症

    佐々木崇, 椿下早絵, 菊池賢, 田中良和, 金子純高, 鎌田信一, 平松啓一, 平松啓一

    日本獣医皮膚科学会学術大会・総会   12th   2009

  • Streptococcus intermedius NCDO 2227Tの全ゲノム解析

    菊池 賢, 馬場 理, 佐々木 崇, 岸井 こずゑ, 渡邊 真弥, 関根 美和, 松尾 美樹, 崔 龍洙, 伊藤 輝代, 平松 啓一

    日本細菌学雑誌   63 ( 1 )   119 - 119   2008.2

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    Ichushi

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  • 薬剤感受性の異なるMRSAに対するフルオロキノロンのPostantibiotic effect

    星最智, 菊池賢, 佐々木崇, 外園千恵, 木下茂, 平松啓一

    角膜カンファランス・日本角膜移植学会プログラム・抄録集   32nd-24th   2008

  • 馬の鼻腔内および感染部位から分離したブドウ球菌について

    椿下早絵, 三浦久延, 佐々木崇, 桑原京子, 平松啓一

    北海道獣医師会雑誌   52 ( 8 )   2008

  • イヌにおけるメチシリン耐性Staphylococcus pseudinthermedius(MRSP)の広がり

    佐々木崇, 菊池賢, 高橋並子, 平松啓一, 平松啓一

    日本細菌学雑誌   62 ( 1 )   2007

  • 日本獣医生命科学大学付属動物医療センターにおけるメチシリン耐性ブドウ球菌サーベイランス

    佐々木崇, 菊池賢, 田中良和, 鎌田信一, 平松啓一, 平松啓一

    日本獣医学会学術集会講演要旨集   144th   2007

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Presentations

  • 抗菌薬外用剤は意味があるのか? Invited

    佐々木崇

    第6回日本獣医耳科研究会 特別講演  2014.10 

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  • 犬の表在性膿皮症におけるクロルヘキシジン外用療法とセファレキシン全身療法の治療効果比較 Invited

    佐々木崇, 山崎真大, 原田和記, 伊従慶太, 山岸建太郎, 永田雅彦, 西藤公司, 加納塁

    第27回日本獣医皮膚科学会学術大会・総会  2024.3 

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  • 伴侶動物におけるブドウ球菌感染症の実態 Invited

    佐々木崇

    第59回日本ブドウ球菌研究会 教育講演  2014.8 

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  • 皮膚科臨床への微生物学的貢献 〜抗菌薬からマイクロバイオームまで〜 Invited

    佐々木崇

    第20回日本獣医皮膚科学会学術大会総会 特別講演  2017.3 

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Awards

  • 平成23年度獣医臨床皮膚科優秀論文賞

    2012.3   日本獣医皮膚科学会   健康な犬におけるメチシリン耐性Staphylococcus pseudintermedius(MRSP)の疫学調査

    須藤哲長, 寺井陽子, 三枝早苗, 椿下早絵, 佐々木崇, 平松啓一

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  • 平成22年度獣医臨床皮膚科優秀論文賞

    2011.3   日本獣医皮膚科学会   臨床検査機関でメチシリン耐性黄色ブドウ球菌(MRSA)と同定された犬由来ブドウ球菌株の分類学的再検討

    笠井智子, 三枝早苗, 佐々木崇

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Research Projects

  • 犬の炎症性腸疾患の幹細胞治療に最適な間葉系幹細胞の探究

    Grant number:25K02182  2025.4 - 2029.3

    日本学術振興会  科学研究費助成事業  基盤研究(B)

    手嶋 隆洋, 道下 正貴, 佐々木 崇

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    Grant amount:\18460000 ( Direct Cost: \14200000 、 Indirect Cost:\4260000 )

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  • イヌ表在性膿皮症におけるセファレキシンへの原点回帰:多剤耐性菌MRSP制御戦略

    Grant number:23K05572  2023.4 - 2026.3

    日本学術振興会  科学研究費助成事業  基盤研究(C)

    佐々木 崇, 西藤 公司, 山崎 真大, 原田 和記

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    Grant amount:\4810000 ( Direct Cost: \3700000 、 Indirect Cost:\1110000 )

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  • Study of inhibitory mechanism of feline infectious peritonitis virus proliferation by calcium antagonist

    Grant number:21H02374  2021.4 - 2024.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)  Grant-in-Aid for Scientific Research (B)

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    Grant amount:\17420000 ( Direct Cost: \13400000 、 Indirect Cost:\4020000 )

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  • Characteristic analysis of canine mesenchymal stem cells capable of differentiating into insulin-producing cells and establishment of transplantation therapy

    Grant number:21H02373  2021.4 - 2024.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)  Grant-in-Aid for Scientific Research (B)

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    Grant amount:\17420000 ( Direct Cost: \13400000 、 Indirect Cost:\4020000 )

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  • Analysis of diversity in tyrosine kinase inhibitor resistance in mast cell tumors toward establishment of individualized therapy

    Grant number:19H03131  2019.4 - 2022.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)  Grant-in-Aid for Scientific Research (B)

    Bonkobara Makoto

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    Grant amount:\17550000 ( Direct Cost: \13500000 、 Indirect Cost:\4050000 )

    This study indicates that accumulation of KIT mutations due to TK inhibitor exposure is important for TK inhibitor resistance in mast cell tumors, which results in TK inhibitor-resistant secondary mutations in KIT. In addition, it was shown that ultra-trace amounts of TK inhibitor-resistant clones may pre-exist in tumor tissues. On the other hand, although various mutations of KIT are detected in canine mast cell tumors, it was not possible to predict whether or not TK inhibitor resistance would occur based solely on the site and type of mutation. Therefore, it was considered that development of highly accurate and extensive genetic analysis system, such as next-generation sequencing analysis, for detection of KIT mutation and further functional characterization the mutant KIT proteins are important in order to establish individualized therapies to overcome TK inhibitor resistance.

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  • Fecal microbiota transplantation for ulcerative colitis

    Grant number:16K09328  2016.4 - 2019.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)  Grant-in-Aid for Scientific Research (C)

    Ishikawa Dai

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    Grant amount:\4680000 ( Direct Cost: \3600000 、 Indirect Cost:\1080000 )

    This was an open label, non-randomized, prospective control study. These patients were diagnosed with active UC, with a Lichtiger’s Clinical Activity Index (CAI) of 5 or more, or with an endoscopic Mayo clinic score of 1 or more, between July 2014 and March 2017. Results: Patients with mild-to-severe active UC (n=55 A-FMT; n=37 AFM) were included in this assessment. Seventy-nine patients completed this assessment (n=46 A-FMT; n=32 AFM). At 4 weeks after treatment, clinical responses in A-FMT were observed in 31 patients {Per Protocol Set (PPS):67.3%}, which was higher than in AFM (PPS:56.2%). Clinical remission was also observed to be higher in A-FMT than in AFM (A-FMT41.3%, AFM18.7%; p=0.06). Endoscopic sum score was associated with clinical responses (Responders7.5±3.2, Non-responders5.1±3.6; p=0.03), and clinical responses and remission were significantly higher in proctitis than in other types of colitis in A-FMT (n=38, 8; p=0.03, p=0.005).

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  • Studies on the mechanisms and therapeutic approach for resistance of tyrosine kinase inhibitors in mast cell tumour

    Grant number:15H04601  2015.4 - 2018.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)  Grant-in-Aid for Scientific Research (B)

    BONKOBARA MAKOTO, TAMURA KYOICHI, ARIIZUMI KIYOSHI, YASUDA AKIKO, SHIGIHARA KAE

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    Grant amount:\17290000 ( Direct Cost: \13300000 、 Indirect Cost:\3990000 )

    The purpose of this study was to investigate the resistance mechanisms and overcoming strategies in tyrosine kinase inhibitor-resistant mast cell tumor. Using imatinib-sensitive canine neoplastic mast cell lines carrying a KIT activating mutation, imatinib-resistant sublines were established by culturing in increasing concentrations of imatinib. From the genetic and protein analysis of the imatinib-resistant sublines, it was considered that the mechanisms including 1) reactivation of KIT by emergence of second mutation in KIT gene, 2) KIT/SFK-independent activation of ERK, 3) overexpression of KIT via prolongation of its life span, or 4) combination of these mechanisms underlay the imatinib resistance in the mast cell lines. Identification of mechanism for imatinib-resistance in individual cases could be important for development of overcoming strategies in tyrosine kinase inhibitor-resistant mast cell tumor.

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  • Therapeutic potential of transferring of Tregs to SAMP1 mice

    Grant number:25860562  2013.4 - 2016.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Grant-in-Aid for Young Scientists (B)  Grant-in-Aid for Young Scientists (B)

    Ishikawa Dai, OSADA Taro, SASAKI Takashi

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    Grant amount:\4160000 ( Direct Cost: \3200000 、 Indirect Cost:\960000 )

    The commensal flora plays an important role in the intestinal inflammation. However, we have recently shown that commensal bacteria are not essential for the development of SAMP1 ileitis. In this study, we demonstrate that cotransfer of SPF CD4+ cells prevent the colitis induced by GF SAMP CD4+ cells. GF nTreg cells indicate lower production of immunoregulatory cytokines in culture stimulation assay and significantly impaired suppressive capacities both in the proliferative responses and in inducing the colitis. GF SAMP mice orally receiving enteric flora from SPF mice develop significant colitis in acute phase due to a defect in nTreg cells, but rapidly expanded Treg cells suppressed later colitis. Furthermore, they prevented developing DSS-induced colitis. Our results provide evidence that the absence of commensal flora lead to impaired functions of nTreg cells, which contributes to the development of colitis but not ileitis in SAMP mice.

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  • ブドウ球菌と哺乳類の共進化

    Grant number:11J10712  2011 - 2013

    日本学術振興会  科学研究費助成事業 特別研究員奨励費  特別研究員奨励費

    佐々木 崇

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    Grant amount:\2400000 ( Direct Cost: \2400000 )

    ブドウ球菌属と哺乳類の共進化関係を明らかにするために、55科、151種、1667個体の哺乳類からブドウ球菌種を分離し種同定を実施した。その結果、霊長類とStaphyloeoeeus aureus group、ローラシア獣類とS. delphini-groupがそれぞれ共進化関係にあることを見いだした。その情報をキャリブレーションポイントとし、ブドウ球菌属全43種および最近縁他属であるMaerococcus easeolyticusの全ゲノム情報から選び出した31のオルソログ遺伝子(重複、水平伝播、incompletelineage sortingの影響を受けていないオルソログ)を用いたアミノ酸配列による分岐年代推定を実施した。ブドウ球菌属の共通祖先が出現したのは約2億3000万年前に遡り、最古の哺乳類化石出土時期と極めて近い年代を示した。また、S. seiurt-groupの分岐以降のStaphylococcus属の共通祖先出現は約1億8000年前に遡ったが、ちょうどその時期、地球上では、哺乳類が有袋類と有胎盤類へと分岐しはじめ、パンゲア大陸の南北への分断が始まっていた。このことから、ブドウ球菌は哺乳類出現とともに地球上に出現し、現生のブドウ球菌種の大部分は有胎盤類と共進化してきたことが示唆された。
    ブドウ球菌属のゲノム進化がどのような方向性をもって進んできたのかを推定するために、Firmicutes門におけるBacillus属、Streptococcus属およびStaphylococcus属の3属間コアゲノム比較を行なった。Staphylococous属は無機イオン輸送関連遺伝子を全種で固く保持し、皮膚組織で激変する浸透圧に耐えうる耐塩性進化を遂げたことがわかった。炭水化物、核酸、アミノ酸、補酵素代謝関連もブドウ球菌属は3属中最も固く保持しており、全種が同一ニッチで共通の代謝活動を営んでいることが示唆された。

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  • コアグラーゼ陽性ブドウ球菌の薬剤耐性と進化

    Grant number:09J09101  2009 - 2010

    日本学術振興会  科学研究費助成事業 特別研究員奨励費  特別研究員奨励費

    佐々木 崇

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    Grant amount:\2400000 ( Direct Cost: \2400000 )

    コアグラーゼ陽性ブドウ球菌(CPS)7菌種は鑑別が難しく、しばしばS. aureus以外のCPSはS. aureusと誤同定されてしまう。そのため、動物におけるCPSの生態の本質は不明のままであった。本研究では、。
    今年度の研究計画である動物由来Staphylococcus aureusクローンの宿主特異性について解析するため、様々な動物からブドウ球菌を分離している。ヒト、コモンマーモセット、スローロリス、ウサギ、チンチラ、モルモット、デグー、ジャンガリアンハムスター、ウシ、ブタ、ウマ、イヌ、タヌキ、キツネ、フェレット、ネコ、ハリネズミ、スンクスなどから分離したS. aureus株に対し、Multilocus sequence typing(MLST)を行たった。そのなかでも特に公衆衛生上人間との関わりの深いイヌおよびネコにおけるS. aureusクロニーンのpopulation genetic structureの解析を行い、多様度、病原性因子保有率およびメチシリン耐性遺伝子保有率を評価した。その結果、イヌはS. aureusおよびMRSAのどのクローンも常在しないことが示唆され、ネコの保菌するS. aureusクローンはヒトとは異なることが示唆された。ネコの感染症起因菌としてのMRSA分離株では、人間でみられるST5(日本国内院内型MRSA)とST8(市中感染型MRSA)の2タイプが全てを占めた。それゆえ、ネコ由来MRSAは人間からの感染であることが示唆された。本結果は現在論文作成中である。
    また、ブドウ球菌属の様々な動物宿主における生態調査を進める過程で、CPSと哺乳類の共進化関係が示唆されたため、「ブドウ球菌と哺乳類の共進化」というテーマで平成23年度学術振興会特別研究員PDに申請し採択されたため、今後も継続して研究を行っていく。

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Teaching Experience

  • 免疫学

    2021.9 Institution:札幌医学技術福祉歯科専門学校

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  • 動物実験の基礎知識

    2017.5 Institution:札幌医科大学

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  • 微生物学

    2016.12 Institution:埼玉大学

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  • 遺伝子検査学実習

    2016 Institution:文京学院大学

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  • 微生物実習、微生物学

    2014.4 - 2017.3 Institution:順天堂大学

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  • 獣医衛生学実習、総合獣医学

    2006.4 - 2017.3 Institution:日本獣医生命科学大学

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