Education 【 display / non-display 】

Education 【 display / non-display 】

• 2015

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  Now

  Sapporo Medical University   医学部   感染制御・臨床検査医学講座  

• 1992

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  2015

  Sapporo Medical University   医学部   泌尿器科学講座  

• 　

  -

  1992

  Sapporo Medical University  

Degree 【 display / non-display 】

Degree 【 display / non-display 】

• 1, Bactericidal effect of levofloxacin on strains with equal susceptibility in an in vitro urinary bladder model. 2, Changes in susceptibility of Pseudomonas aeruginosa to gatifloxacin and carbapenem in an in vitro urinary bladder model.

Professional Memberships 【 display / non-display 】

Professional Memberships 【 display / non-display 】

• 2015

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  Now

  Japanese Society of Laboratory Medicine

• 2015

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  Now

  The Japan Association for Clinical Laboratory Science

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  American Sexually Transmitted Diseases Association

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  Japanese Association for Infectious Diseases

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  Japanese Society of Endourology and ESWL

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Research Areas 【 display / non-display 】

Research Areas 【 display / non-display 】

• Life sciences   Infectious disease  

Affiliation 【 display / non-display 】

Affiliation 【 display / non-display 】

• Sapporo Medical University   School of Medicine, Department of Infection Control and Laboratory Medicine  

Research Interests 【 display / non-display 】

Research Interests 【 display / non-display 】

• Urinary tract infection, sexually transmitted infection, clinical laboratory medicine

Papers 【 display / non-display 】

Papers 【 display / non-display 】

• Affinity of β-Lactam Antibiotics for Neisseria gonorrhoeae Penicillin-Binding Protein 2 Having Wild, Cefixime-Reduced-Susceptible, and Cephalosporin (Ceftriaxone)-Resistant penA Alleles.

  Yoshiki Hiyama, Soh Yamamoto, Toyotaka Sato, Noriko Ogasawara, Naoya Masumori, Satoshi Takahashi, Shin-Ichi Yokota

  Microbial drug resistance (Larchmont, N.Y.)    2024.01  [International journal]

  　View Summary

  Multidrug-resistant Neisseria gonorrhoeae is a serious concern worldwide. Resistance to β-lactam antibiotics occurs through mutations in penicillin-binding proteins (PBPs), acquisition of β-lactamases, and alteration of antibiotic penetration. Mosaic structures of penA, which encodes PBP2, play a major role in resistance to β-lactams, especially cephalosporins. Ceftriaxone (CRO) is recognized as the only satisfiable antibiotic for the treatment of gonococcal infections; however, CRO-resistant isolates have emerged in the community. Here, we examined the affinity of β-lactam antibiotics for recombinant PBP2 in a competition assay using fluorescence-labeled penicillin. We found no or little difference in the affinities of penicillins and meropenem (MEM) for PBP2 from cefixime (CFM)-reduced-susceptible strain and cephalosporin-resistant strain. However, the affinity of cephalosporins, including CRO, for PBP2 from the cephalosporin-resistant strain was markedly lower than that for PBP2 from the CFM-reduced-susceptible-resistant strain. Notably, piperacillin (PIP) showed almost the same affinity for PBP2 from penicillin-susceptible, CFM-reduced-susceptible, and cephalosporin (including CRO)-resistant strains. Thus, PIP/tazobactam and MEM are candidate antibiotics for the treatment of CRO-resistant/multidrug-resistant N. gonorrhoeae.

  DOI PubMed

• High prevalence of colistin heteroresistance in specific species and lineages of Enterobacter cloacae complex derived from human clinical specimens.

  Shota Fukuzawa, Toyotaka Sato, Kotaro Aoki, Soh Yamamoto, Noriko Ogasawara, Chie Nakajima, Yasuhiko Suzuki, Motohiro Horiuchi, Satoshi Takahashi, Shin-Ichi Yokota

  Annals of clinical microbiology and antimicrobials   22 ( 1 ) 60 - 60  2023.07  [International journal]

  　View Summary

  BACKGROUND: Colistin (CST) is a last-line drug for multidrug-resistant Gram-negative bacterial infections. CST-heteroresistant Enterobacter cloacae complex (ECC) has been isolated. However, integrated analysis of epidemiology and resistance mechanisms based on the complete ECC species identification has not been performed. METHODS: Clinical isolates identified as "E. cloacae complex" by MALDI-TOF MS Biotyper Compass in a university hospital in Japan were analyzed. Minimum inhibitory concentrations of CST were determined by the broth microdilution method. The population analysis profiling (PAP) was performed for detecting the heteroresistant phenotype. The heat shock protein 60 (hsp60) cluster was determined from its partial nucleotide sequence. From the data of whole-genome sequencing, average nucleotide identity (ANI) for determining ECC species, multilocus sequence type, core genome single-nucleotide-polymorphism-based phylogenetic analysis were performed. phoPQ-, eptA-, and arnT-deleted mutants were established to evaluate the mechanism underlying colistin heteroresistance. The arnT mRNA expression levels were determined by reverse transcription quantitative PCR. RESULTS: Thirty-eight CST-resistant isolates, all of which exhibited the heteroresistant phenotype by PAP, were found from 138 ECC clinical isolates (27.5%). The prevalence of CST-resistant isolates did not significantly differ among the origin of specimens (29.0%, 27.8%, and 20.2% for respiratory, urine, and blood specimens, respectively). hsp60 clusters, core genome phylogeny, and ANI revealed that the CST-heteroresistant isolates were found in all or most of Enterobacter roggenkampii (hsp60 cluster IV), Enterobacter kobei (cluster II), Enterobacter chuandaensis (clusters III and IX), and Enterobacter cloacae subspecies (clusters XI and XII). No heteroresistant isolates were found in Enterobacter hormaechei subspecies (clusters VIII, VI, and III) and Enterobacter ludwigii (cluster V). CST-induced mRNA upregulation of arnT, which encodes 4-amino-4-deoxy-L-arabinose transferase, was observed in the CST-heteroresistant isolates, and it is mediated by phoPQ pathway. Isolates possessing mcr-9 and mcr-10 (3.6% and 5.6% of total ECC isolates, respectively) exhibited similar CST susceptibility and PAP compared with mcr-negative isolates. CONCLUSIONS: Significant prevalence (approximately 28%) of CST heteroresistance is observed in ECC clinical isolates, and they are accumulated in specific species and lineages. Heteroresistance is occurred by upregulation of arnT mRNA induced by CST. Acquisition of mcr genes contributes less to CST resistance in ECC.

  DOI PubMed

• Colistin-resistant bacteria poses few risks under physiological conditions

  Soh Yamamoto, Masaru Usui, Noriko Ogasawara, Wataru Hayashi, Masato Suzuki, Noriyuki Nagano, Chie Nakajima, Yasuhiko Suzuki, Motohiro Horiuchi, Satoshi Takahashi, Shin-ichi Yokota, Yutaka Tamura, Toyotaka Sato

  Research Square ( Research Square Platform LLC )   2023.06

  　View Summary

  Abstract Globally, 5.0 million people die annually from infections associated with antimicrobial-resistant bacteria, most commonly Escherichia coli¹. As colistin is a last-resort antibiotic for multidrug-resistant bacterial infections, the global spread of plasmid-mediated colistin resistance genes (mcr) gene is considered a major public health risk^2-4. However, the actual health risks of colistin resistance in hazardous bacteria have never been evaluated under physiological conditions. Here, we show that the fitness/virulence and colistin resistance of the pandemic multidrug-resistant E. coli clone ST131⁵ very depending on the acquired colistin resistance determinants and differ between physiological and in vitro conditions. The fitness/virulence of ST131 was unaffected by chromosomal-gene (pmrB) mutations or the acquisition of mcr-5-harbouring plasmids in mouse models. However, the acquisition of mcr-1- or mcr-3-harbouring plasmids attenuated fitness/virulence and promoted colistin susceptibility in human serum. We identified two virulence attenuation factors (vafA and vafB) on the pIncI2_mcr-1 plasmid that hijacked the ST131 transcriptome and inhibited nucleotide synthesis, attenuating colistin resistance. Our results demonstrate that colistin resistance poses much less of a threat than believed^6,7. We suggest that “nonresistance genes,” rather than resistance genes, are important antimicrobial resistance determinants for human health because they determine fitness/virulence and ultimately antimicrobial susceptibility under physiological conditions.

  DOI

• ゲノム解析は同時期に複数病棟で発生したCOVID-19クラスター事例の全体像の把握に有用である

  藤谷 好弘, 中江 舞美, 中村 広士, 富樫 篤生, 齋藤 充史, 黒沼 幸治, 高橋 聡, 大久保 和洋, 川代 愛梨, 田宮 和真

  日本環境感染学会総会プログラム・抄録集 ( (一社)日本環境感染学会 )  38回   271 - 271  2023.06

• Pseudo-outbreak of Mycobacterium lentiflavum at a general hospital in Japan.

  Yutaro Nagano, Koji Kuronuma, Yasuo Kitamura, Kanami Nagano, Hayato Yabe, Sayaka Kudo, Toyotaka Sato, Shinya Nirasawa, Mami Nakae, Motohiro Horiuchi, Shin-Ichi Yokota, Yoshihiro Fujiya, Atsushi Saito, Satoshi Takahashi, Hirofumi Chiba

  Infection control and hospital epidemiology     1 - 7  2023.04  [International journal]

  　View Summary

  BACKGROUND: Mycobacterium lentiflavum is a slow-growing nontuberculous mycobacterium that is widely distributed in soil and water systems, but it is sometimes pathogenic to humans. Although cases of M. lentiflavum infections are rare, 22 isolates of M. lentiflavum were identified at a single hospital in Japan. We suspected a nosocomial outbreak; thus, we conducted transmission pattern and genotype analyses. METHODS: Cases of M. lentiflavum isolated at Kushiro City General Hospital in Japan between May 2020 and April 2021 were analyzed. The patient samples and environmental culture specimens underwent whole-genome sequencing (WGS). Additionally, we retrospectively collected clinical data from patient medical records. RESULTS: Altogether, 22 isolates of M. lentiflavum were identified from sputum and bronchoalveolar lavage samples. Clinically, the instances with M. lentiflavum isolates were considered contaminants. In the WGS analysis, 19 specimens, including 18 patient samples and 1 environmental culture from the hospital's faucet, showed genetic similarity. The frequency of M. lentiflavum isolation decreased after we prohibited the use of taps where M. lentiflavum was isolated. CONCLUSIONS: WGS analysis identified that the cause of M. lentiflavum pseudo-outbreak was the water used for patient examinations, including bronchoscopy.

  DOI PubMed

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Misc 【 display / non-display 】

Misc 【 display / non-display 】

• COVID-19ワクチン接種後感染者1事例の抗体獲得推移

  中江 舞美, 藤谷 好弘, 藤居 賢, 黒沼 幸治, 高橋 聡

  日本環境感染学会総会プログラム・抄録集 ( (一社)日本環境感染学会 )  36回   311 - 311  2021.09

• 新型コロナウイルス感染症専用病棟の職員の感染リスクにかかる後向きコホート研究

  藤谷 好弘, 中江 舞美, 中村 広士, 黒沼 幸治, 高橋 聡

  日本環境感染学会総会プログラム・抄録集 ( (一社)日本環境感染学会 )  36回   303 - 303  2021.09

• 鼻腔ぬぐい液および抗原定量検査の臨床的有効性に関する検討

  藤谷 好弘, 黒沼 幸治, 高橋 聡

  感染症学雑誌 ( (一社)日本感染症学会 )  95 ( 臨増 ) 251 - 251  2021.04

• 流産手術後に長期間の反復菌血症を呈しミュンヒハウゼン症候群が疑われた1例

  真里谷 奨, 長井 陽子, 藤谷 好弘, 黒沼 幸治, 高橋 聡

  感染症学雑誌 ( (一社)日本感染症学会 )  95 ( 臨増 ) 288 - 288  2021.04

• 新型コロナウイルス感染症におけるファビピラビル投与の評価

  伊部 裕太, 藤居 賢, 石郷 友之, 國本 雄介, 藤谷 好弘, 黒沼 幸治, 高橋 聡

  日本化学療法学会雑誌 ( (公社)日本化学療法学会 )  69 ( Suppl.A ) 254 - 254  2021.04

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Awards 【 display / non-display 】

Awards 【 display / non-display 】

• 北海道医師会賞・北海道知事賞

  2018.10   北海道医師会・北海道  

• 第98回日本泌尿器科学会 総会賞

  2010.04  

• 第24回稲田賞

  2006   泌尿器科紀要  

• 第365回日本泌尿器科学会北海道地方会 地方会賞

  2005   日本泌尿器科学会北海道地方会  

• 平成14年度日本抗生物質学術協議会・ファイザー感染症研究助成（海外留学助成）

  2002   日本抗生物質学術協議会  

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Research Projects 【 display / non-display 】

Research Projects 【 display / non-display 】

• 淋菌薬剤感受性サーベイランスによる薬剤耐性淋菌に対する有効な抗菌化学療法の検討

  基盤研究(C)

  Project Year :

  2022.04

  -

  2025.03

   

  安田 満, 高橋 聡, 佐藤 勇樹

• Epidemiological and therapeutical study of pathogens associated to non-gonococcal urethritis

  Grant-in-Aid for Scientific Research (B)

  Project Year :

  2013.04

  -

  2016.03

   

  MATSUMOTO TETSURO, HAMASUNA Ryoichi, TAKAHASHI Satoshi, FUKUDA Kazumasa

  　View Summary

  From the specimens of male urethritis, many kinds of microorganisms are detected, but the pathogenicities of microorganisms except for N. gonorrhoeae or C. trachomatis has not been determined. As the new approach, the clone library method was used for analysis of microorganisms of urethritis. This method added quantitative concept to qualitative PCR methods. By this method, the pathogenicities of N. gonorrhoeae adn M. genitalium to the male urethra was confirmed. In addition, it was found that H. influenzae and N. meningitidis would be possible pathogens for male urethritis. By the examination of microorganisms in the oral cavities of patients with male urethritis, it was found that causative bacteria of male urethritis and bacteria of the resident flora in the vagina were detected in the oral cavities of male patients. these indicated that oral sex is closely related to STIs. When we treat male urethritis, we have to eradicate microorganisms in both the urethra and oral cavities.

• Evaluation of stanniocalcin-1 and NADPH oxidase as marker of metastasis in breast cancer

  Grant-in-Aid for Scientific Research (C)

  Project Year :

  2012.04

  -

  2016.03

   

  TANAKA MAKI, TAKAHASHI SATOSHI, KOBAYASHI DAISUKE, WATANABE NAOKI, KURIBAYASHI KAGEAKI

  　View Summary

  In this study, we aimed to evaluate potential marker of metastasis in breast cancer. Reactive oxygen species, produced from NADPH oxidase (NOX), affect cancer metastasis and accelerate cell migration. Stanniocalcin-1 (STC-1), a regulator of calcium metabolism, is highly expressed in tumor cells. Therefore, we focused our research on calcium-dependent NOX5 and STC-1 molecules. High levels of STC-1 in breast cancer cells accelerated cell motility and enhanced lung metastasis in mice. However, no difference in cell migration was observed with high levels of NOX5. Thus, we conclude that STC-1 enhances the metastatic potential of breast cancer cells and our results suggest that STC-1 may have utility as a novel prediction marker of metastasis.

• Clinical study on the effect of androgen to organs other genitalis

  Grant-in-Aid for Scientific Research (C)

  Project Year :

  2007

  -

  2008

   

  KOBAYASHI Ko, MASUMORI Naoya, TAKAHASHI Satoshi

  　View Summary

  Androgenの減少は骨に対しては代謝の亢進につながることが明らかとなったが、短期間では骨粗鬆症の発症のレベルまでは骨密度の減少はなかった。握力などの筋力には経過中に変化を認めなかった。メタボリック症候群で注目される物質のひとつであるアディポネクチンも経過中は両群に変化を認めなかった。脳に対する影響として、認知障害の有無をミニメンタルステート検査を行ったが経過中に両群とも変化は確認できず、認知能に対する影響は確認できなかった。このように、アンドロゲンの低下が早期より影響を及ばす臓器としては生殖器以外では骨が注目される結果であった。

• The relationship of the inflammatory infiltrating cell in prostate grand and chemokine

  Grant-in-Aid for Scientific Research (C)

  Project Year :

  2001

  -

  2003

   

  ITOH Naoki, TAKAHASHI Satoshi, MASUMORI Naoya, TSUKAMOTO Taiji, HOTTA Hiroshi

  　View Summary

  (1)The pathological study of inflammatory cell infiltration in the prostate in patients Patients entered into the study received radical cystoprostatectomy because of invasive bladder cancer in our institute from 1998 to 2000. The infiltrating cell type was assessed by immunostaining using a series of antibodies CD2O, CD45RO, CD68,S-100. The types of infiltrating cells were dominantly T cells. Inflammatory cell infiltration was seen in 32.4% cases. (2)Antimicrobial agents and suppression of cytokine secretion of prostate cancer cell line. PC-3,a human prostate cancer cell lines, was used for the experiment. IL-8 concentrations of the supematants were increased depending on the concentrations of Mycoplasma hominis. The mRNA of Toll like receptor-2 and Toll like receptor4 were demonstrated by RT-PCR in PC-3 cell lines. The activities of NF-κB were increased depending on the concentration of Mycoplasma hominisa. These data show that the signals from Toll-like receptor up the activities of NF-κB and lead to produce of IL-8. The influence of GFLX on IL-8 mRNA expression was analyzed using RT-PCR. GFLX significantly attenuated the TNF-α induced IL-8 mRNA level. GFLX suppresses the secretion of IL-8 from PC-3 in a dose-dependent manner. The results may imply that GFLX has an anti-inflammatory effect on chronic prostatitis.

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