Details of a Researcher - YOKOTA Shinichi

Papers - YOKOTA Shinichi

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Isolation of a mcr-1-harbouring Escherichia coli isolate from a human clinical setting in Sapporo, Japan.

Toyotaka Sato, Akira Fukuda, Masaru Usui, Masaaki Shinagawa, Tsukasa Shiraishi, Yutaka Tamura, Satoshi Takahashi, Shin-Ichi Yokota

Journal of global antimicrobial resistance 13 20 - 21 2018.06 [Refereed] [International journal]

DOI PubMed

Release of large amounts of lipopolysaccharides from Pseudomonas aeruginosa cells reduces their susceptibility to colistin.

Shin-Ichi Yokota, Hiroshi Hakamada, Soh Yamamoto, Toyotaka Sato, Tsukasa Shiraishi, Masaaki Shinagawa, Satoshi Takahashi

International journal of antimicrobial agents 51 ( 6 ) 888 - 896 2018.06 [Refereed] [International journal]

Pseudomonas aeruginosa is an important etiological agent of opportunistic infections. Injectable colistin is available as a last-line treatment option for multidrug-resistant P. aeruginosa infections. When cells were inoculated at a high number, colistin-susceptible P. aeruginosa grew on agar medium containing colistin at a concentration 10-fold higher than the minimum inhibitory concentration without acquiring colistin resistance. This study examined the responsible mechanism for growth in the presence of a high concentration of colistin. Cell wash fluid derived from P. aeruginosa efficiently reduced colistin antimicrobial activity. This reduction was mediated by lipopolysaccharide (LPS) in the wash fluid. Extracellular LPS inhibited colistin activity more effectively than cell-bound LPS in fixed cells. Cell wash fluids from Escherichia coli and Acinetobacter baumannii also reduced colistin activity; however, they were less potent than those from P. aeruginosa. The amount of LPS in cell wash fluid from P. aeruginosa was approximately 10-fold higher than that in fluid from E. coli or A. baumannii. In conclusion, cell-free LPS derived from bacterial cells inhibited the antimicrobial activity of colistin, and this effect was greatest for P. aeruginosa. Thus, large amounts of broken and dead cells of P. aeruginosa at infection foci will reduce the effectiveness of colistin, even against cells that have not yet acquired resistance.

DOI PubMed

Evaluation of consistency in quantification of gene copy number by real-time reverse transcription quantitative polymerase chain reaction and virus titer by plaque-forming assay for human respiratory syncytial virus.

Keisuke Yamamoto, Noriko Ogasawara, Soh Yamamoto, Kenichi Takano, Tsukasa Shiraishi, Toyotaka Sato, Hiroyuki Tsutsumi, Tetsuo Himi, Shin-Ichi Yokota

Microbiology and immunology 62 ( 2 ) 90 - 98 2018.02 [Refereed] [International journal]

The plaque-forming assay is the standard technique for determining viral titer, and a critical measurement for investigating viral replication. However, this assay is highly dependent on experimental technique and conditions. In the case of human respiratory syncytial virus (RSV) in particular, it can be difficult to objectively confirm the accuracy of plaque-forming assay because the plaques made by RSV are often small and unclear. In recent studies, RT-qPCR methods have emerged as a supportive procedure for assessment of viral titer, yielding highly sensitive and reproducible results. In this report, we compare the viral replication, as determined by plaque-forming assay, and the copy numbers of RSV genes NS1, NS2, N, and F, as determined by RT-qPCR. Two real-time PCR systems, SYBR Green and TaqMan probe, gave highly similar results for measurement of copy numbers of RSV N genes of virus subgroups A. We determined the RSV gene copy numbers in the culture cell supernatant and cell lysate measured at various multiplicities of infection. We found that copy number of the RSV N gene in the culture supernatant and cell lysate was highly correlated with plaque-forming units. In conclusion, RT-qPCR measurement of RSV gene copy number was highly dependent on viral titer, and the detailed comparison between each gene copy number and virus titer should be useful and supportive in confirming RSV plaque-forming assay and virus dynamics. The technique may also be used to estimate the amount of RSV present in clinical specimens.

DOI PubMed

High prevalence of mcr-1, mcr-3 and mcr-5 in Escherichia coli derived from diseased pigs in Japan.

Akira Fukuda, Toyotaka Sato, Masaaki Shinagawa, Satoshi Takahashi, Tetsuo Asai, Shin-Ichi Yokota, Masaru Usui, Yutaka Tamura

International journal of antimicrobial agents 51 ( 1 ) 163 - 164 2018.01 [Refereed] [International journal]

DOI PubMed

Tigecycline susceptibility of Klebsiella pneumoniae complex and Escherichia coli isolates from companion animals: the prevalence of tigecycline-nonsusceptible K. pneumoniae complex, including internationally expanding human pathogenic lineages

Sato T, Harada K, Usui M, Tsuyuki Y, Shiraishi T, Tamura Y, Yokota S

Microbial Drug Resistance 24 ( 6 ) 860 - 867 2018 [Refereed]

Lipoteichoic acids are embedded in cell walls during logarithmic phase, but exposed on membrane vesicles in Lactobacillus gasseri JCM 1131T

T. Shiraishi, S. Yokota, Y. Sato, T. Ito, S. Fukiya, S. Yamamoto, T. Sato, A. Yokota

Beneficial Microbes ( Wageningen Academic Publishers ) 9 ( 4 ) 653 - 662 2018 [Refereed]

Lipoteichoic acid (LTA) is a cell surface molecule specific to Gram-positive bacteria. How LTA localises on the cell surface is a fundamental issue in view of recognition and immunomodulation in hosts. In the present study, we examined LTA localisation using strain JCM 1131T of Lactobacillus gasseri, which is a human intestinal lactic acid bacterium, during various growth phases by immunoelectron microscopy. We first evaluated the specificity of anti-LTA monoclonal antibody clone 55 used as a probe. The glycerophosphate backbone comprising almost intact size (20 to 30 repeating units) of LTA was required for binding. The antibody did not bind to other cellular components, including wall-teichoic acid. Immunoelectron microscopy indicated that LTA was embedded in the cell wall during the logarithmic phase, and was therefore not exposed on the cell surface. Similar results were observed for Lactobacillus fermentum ATCC 9338 and Lactobacillus rhamnosus ATCC 7469T. By contrast, membrane vesicles were observed in the logarithmic phase of L. gasseri with LTA exposed on their surface. In the stationary and death phases, LTA was exposed on cell wall-free cell membrane generated by autolysis. The dramatic alternation of localisation in different growth phases and exposure on the surface of membrane vesicles should relate with complicated interaction between bacteria and host.

DOI

Complete Genome Sequence of Multidrug-Resistant Streptococcus pneumoniae Serotype 19F Isolated from an Invasive Infection in Sapporo, Japan.

Toyotaka Sato, Yasuo Ohkoshi, Takayuki Wada, Yukari Fukushima, Hiromi Murabayashi, Yasunari Takakuwa, Kaoru Nishiyama, Tsukasa Shiraishi, Chie Nakajima, Yasuhiko Suzuki, Shin-Ichi Yokota

Genome announcements 5 ( 44 ) e01239-17 2017.11 [Refereed] [International journal]

DOI PubMed

The role of transcriptional factor p63 in regulation of epithelial barrier and ciliogenesis of human nasal epithelial cells

Yakuto Kaneko, Takayuki Kohno, Takuya Kakuki, Ken-ichi Takano, Noriko Ogasawara, Ryo Miyata, Shin Kikuchi, Takumi Konno, Tsuyoshi Ohkuni, Ryoto Yajima, Akito Kakiuchi, Shin-ichi Yokota, Tetsuo Himi, Takashi Kojima

SCIENTIFIC REPORTS ( NATURE PUBLISHING GROUP ) 7 ( 1 ) 10935 2017.09 [Refereed]

Disruption of nasal epithelial tight junctions (TJs) and ciliary dysfunction are found in patients with chronic rhinosinusitis (CRS) and nasal polyps (NPs), along with an increase of p63-positive basal cells and histone deacetylase (HDAC) activity. To investigate these mechanisms, primary cultures of HNECs transfected with human telomerase reverse transcriptase (hTERT-HNECs) were transfected with siRNAs of TAp63 and Delta Np63, treated with the NF-kB inhibitor curucumin and inhibitors of HDACs, and infected with respiratory syncytial virus (RSV). In TERT-HNECs, knockdown of p63 by siRNAs of TAp63 and Delta Np63, induced claudin-1 and -4 with Sp1 activity and enhanced barrier and fence functions. The knockdown of p63 enhanced the number of microvilli with the presence of cilia-like structures. Treatment with curcumin and inhibitors of HDACs, or infection with RSV prevented expression of p63 with an increase of claudin-4 and the number of microvilli. The knockdown or downregulation of p63 inhibited phospho-p38MAPK, and the p38MAPK inhibitor downregulated p63 and upregulated the barrier function. Thus, epithelial barrier and ciliogenesis of nasal epithelium are regulated in a p63-negative manner in normal and upper airway diseases. Understanding of the regulation of p63/p38 MAPK/NF-kappa B may be important in the therapy for airway allergy and its drug delivery system.

DOI

Mycoplasma bovis isolates from dairy calves in Japan have less susceptibility than a reference strain to all approved macrolides associated with a point mutation (G748A) combined with multiple species-specific nucleotide alterations in 23S rRNA

Toyotaka Sato, Hidetoshi Higuchi, Shin-ichi Yokota, Yutaka Tamura

MICROBIOLOGY AND IMMUNOLOGY ( WILEY ) 61 ( 6 ) 215 - 224 2017.06 [Refereed]

Erythromycin, tylosin and tilmicosin are approved for use in cattle in Japan, the latter two being used to treat Mycoplasma bovis infection. In this study, 58M. bovis isolates obtained from Japanese dairy calves all exhibited reduced susceptibility to these macrolides, this widespread reduced susceptibility being attributable to a few dominant lineages. All 58 isolates contained the G748A variant in both the rrl3 and rrl4 alleles of 23S rRNA, whereas a reference strain (PG45) did not. G748 localizes in the central loop of domain II (from C744 to A753) of 23S rRNA, which participates in binding to mycinose, a sugar residue present in both tylosin and tilmicosin. A number of in vitro-selected mutants derived from M. bovis PG45 showed reduced susceptibility to tylosin and tilmicosin and contained a nucleotide insertion within the central loop of domain II of rrl3 (U747-G748Ins_CU/GU or A743-U744Ins_UA), suggesting that mutations around G748 confer this reduced susceptibility phenotype. However, other Mycoplasma species containing G748A were susceptible to tylosin and tilmicosin. Sequence comparison with Escherichia coli revealed that M. bovis PG45 and isolates harbored five nucleotide alterations (U744C, G745A, U746C, A752C and A753G) in the central loop of domain II of 23S rRNA, whereas other Mycoplasma species lacked at least two of these five nucleotide alterations. It was therefore concluded that G748 mutations in combination with species-specific nucleotide alterations in the central loop of domain II of 23S rRNA are likely sufficient to reduce susceptibility of M. bovis to tylosin and tilmicosin.

DOI

Novel antimicrobial activities of a peptide derived from a Japanese soybean fermented food, Natto, against Streptococcus pneumoniae and Bacillus subtilis group strains

Manabu Kitagawa, Tsukasa Shiraishi, Soh Yamamoto, Ryosuke Kutomi, Yasuo Ohkoshi, Toyotaka Sato, Hideki Wakui, Hideaki Itoh, Atsushi Miyamoto, Shin-ichi Yokota

AMB EXPRESS ( BIOMED CENTRAL LTD ) 7 127 2017.06 [Refereed]

We recently isolated a tumoricidal peptide from Natto, a Japanese traditional fermented food. In the present study, antimicrobial activity of the Natto peptide was examined. The peptide consisted of 45 amino acid residues, and its structure was predicted to be rich in alpha-helix. It excreted antimicrobial activity only against Streptococcus pneumoniae and Bacillus subtilis group (B. subtilis, Bacillus pumilus, and Bacillus licheniformis). Lesser antimicrobial activity was observed for Streptococcus species other than S. pneumoniae. Hemolysate or hemin was required for the antimicrobial activity of the peptide. The Natto peptide damages the cell membrane of B. subtilis. On the other hand, chain morphology was induced in S. pneumoniae, which is naturally diplococcus, during the early phases of the Natto peptide treatment; following that the cells were rapidly lysed. This suggested that the Natto peptide displayed a novel narrow spectrum of bactericidal activity and inhibited cell separation during cell division of S. pneumoniae.

DOI

Involvement of herpes simplex virus type 1 UL13 protein kinase in induction of SOCS genes, the negative regulators of cytokine signaling

Yuka Sato, Tetsuo Koshizuka, Kei Ishibashi, Koichi Hashimoto, Ken Ishioka, Kazufumi Ikuta, Shin-ichi Yokota, Nobuhiro Fujii, Tatsuo Suzutani

MICROBIOLOGY AND IMMUNOLOGY ( WILEY ) 61 ( 5 ) 159 - 167 2017.05 [Refereed]

The suppressor of cytokine signaling (SOCS) family has eight members and suppresses various cytokine signaling pathways, including IFN signaling. Therefore, some viruses have evolved molecular mechanisms for inducing SOCS proteins and thus escaping host immunity. Herpes simplex virus type 1 (HSV-1) has a mechanism for escaping from type I IFN by induction of both SOCS1 and SOCS3. In this study, expression of the eight members of the SOCS family stimulated by HSV-1 infection was comparatively analyzed by qRT-PCR. It was found that SOCS1 and SOCS3 are induced by HSV-1-infection at 4 hr post infection. However, such induction was not observed in UL13 deficient virus-infected cells, suggesting that UL13 protein kinase participates in induction of both genes. The transcription factor Sp1-binding sites of SOCS3 promoter/enhancer region were identified as the regulatory elements for induction of SOCS3 in HSV-1 infected cells. Accumulation of activated Sp1 was detectable in the nuclei of HSV-1-infected cells before induction of SOCS3. Taken together, these results suggest that HSV-1 has a potent mechanism for escaping from the IFN system.

DOI

マクロライド作用機序クラリスロマイシンの炎症反応修飾作用の分子機構の解明気道上皮細胞のクラリスロマイシン結合タンパク質の同定と機能解析

横田伸一, 山本聡, 小笠原徳子, 植村知加, 高谷芳明, 伊藤英晃, 山本圭佑, 白石宗, 佐藤豊孝, 氷見徹夫

The Japanese Journal of Antibiotics ( (公財)日本感染症医薬品協会 ) 70 ( Suppl.A ) 60 - 64 2017.03

ウイルス、細菌、真菌クラリスロマイシンは気道上皮細胞でRSウイルスによって誘導されるインターフェロンの産生をIRF-3を介して調整する

山本圭佑, 小笠原徳子, 山本聡, 堤裕幸, 氷見徹夫, 横田伸一

The Japanese Journal of Antibiotics ( (公財)日本感染症医薬品協会 ) 70 ( Suppl.A ) 19 - 24 2017.03

患者の手術で採取した鼻粘膜から作製したhTERT導入鼻粘膜上皮細胞(hTERT-HNEC)、肺胞上皮由来細胞株(A549)、ヒト気道上皮細胞株(BEAS-2B)を用い、ヒト気道上皮細胞における急性呼吸器ウイルス感染症に対するクラリスロマイシン(CAM)の効果と、CAMのもつ免疫調節効果のメカニズムを調べるため各種検討した。RSウイルス(RSV)感染のCAMの影響を調べ、CAMがRSV増殖に影響を与えないことが示唆された。hTERT-HNEC、A549、BEAS-2Bなどの気道上皮細胞においてPoly:C処置、RSV感染で誘導されるIFN-β、IFN-λがCAMにより強く抑制された。宿主の自然免疫に関わる転写因子IRF、NF-κB、AP-1の結合領域を含むプロモーター活性化がCAMにより強く抑制された。

Mitochondrial proteins NIP-SNAP-1 and-2 are a target for the immunomodulatory activity of clarithromycin, which involves NF-kappa B-mediated cytokine production

Soh Yamamoto, Noriko Ogasawara, Keisuke Yamamoto, Chika Uemura, Yoshiaki Takaya, Tsukasa Shiraishi, Toyotaka Sato, Shin Hashimoto, Hiroyuki Tsutsumi, Kenichi Takano, Tetsuo Himi, Shin-ichi Yokota

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS ( ACADEMIC PRESS INC ELSEVIER SCIENCE ) 483 ( 3 ) 911 - 916 2017.02 [Refereed]

Macrolide antibiotics have immunomodulatory activities, including suppression of cytokine production, cell adhesion molecule expression, and mucin production. These immunomodulatory activities improve the symptoms of respiratory diseases associated with chronic inflammation. However, the underlying molecular mechanism(s) is not well understood yet. To address this, we prepared clarithromycin (CAM)-conjugated Sepharose and examined bound cellular proteins by proteome analysis. We identified mitochondrial proteins 4-nitrophenylphosphatase domain and non-neuronal synaptosomal associated protein 25-like protein homolog (NIP-SNAP)-1 and -2 and very long-chain acyl-CoA dehydrogenase (VLCAD) as CAM-binding proteins. Production of proinflammatory cytokines (IL-8 and IL-6) induced by lipopolysaccharides (LPSs) and Pam(3)-CSK4 in human epithelial cell lines BEAS-2B and T24 were suppressed by knockdown of NIP-SNAP -1 or -2, and partly by knockdown of VLCAD. Also, knockdown of NIP SNAP-1 or -2 in various cell lines suppressed LPS-induced expression of IL-8 and IL-6 mRNA and NF-kappa B activity. Thus, CAM suppresses NF-kappa B-mediated proinflammatory cytokine production by interacting with mitochondrial proteins, NIP-SNAP-1 and -2. (C) 2016 The Authors. Published by Elsevier Inc.

DOI

NIP-SNAP-1 and-2 mitochondrial proteins are maintained by heat shock protein 60

Soh Yamamoto, Tomoya Okamoto, Noriko Ogasawara, Shin Hashimoto, Tsukasa Shiraishi, Toyotaka Sato, Keisuke Yamamoto, Hiroyuki Tsutsumi, Kenichi Takano, Testuo Himi, Hideaki Itoh, Shin-ichi Yokota

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS ( ACADEMIC PRESS INC ELSEVIER SCIENCE ) 483 ( 3 ) 917 - 922 2017.02 [Refereed]

NIP-SNAP-1 and -2 are ubiquitous proteins thought to be associated with maintenance of mitochondrial function, neuronal transmission, and autophagy. However, their physiological functions remain largely unknown. To elucidate their functional importance, we screened for proteins that interact with NIP SNAP-1 and -2, resulting in identification of HSP60 and P62/SQSTMI as binding proteins. NIP-SNAP-1 and -2 localized in the mitochondrial inner membrane space, whereas HSP60 localized in the matrix. Native gel electrophoresis and filter trap assays revealed that human HSP60 prevented aggregation of newly synthesized NIP-SNAP-2 in an in vitro translation system. Moreover, expression levels of NIP SNAP-1 and -2 in cells were decreased by knockdown of HSP60, but not HSP10. These findings indicate that HSP60 promotes folding and maintains the stability of NIP-SNAP-1 and -2. (C) 2016 Elsevier Inc. All rights reserved.

DOI

Tigecycline Nonsusceptibility Occurs Exclusively in Fluoroquinolone-Resistant Escherichia coli Clinical Isolates, Including the Major Multidrug-Resistant Lineages O25b:H4-ST131-H30R and O1-ST648

Toyotaka Sato, Yuuki Suzuki, Tsukasa Shiraishi, Hiroyuki Honda, Masaaki Shinagawa, Soh Yamamoto, Noriko Ogasawara, Hiroki Takahashi, Satoshi Takahashi, Yutaka Tamura, Shin-ichi Yokota

ANTIMICROBIAL AGENTS AND CHEMOTHERAPY ( AMER SOC MICROBIOLOGY ) 61 ( 2 ) e01654-16 2017.02 [Refereed]

Tigecycline (TGC) is a last-line drug for multidrug-resistant Enterobacteriaceae. We investigated the mechanism(s) underlying TGC nonsusceptibility (TGC resistant/ intermediate) in Escherichia coli clinical isolates. The MIC of TGC was determined for 277 fluoroquinolone-susceptible isolates (ciprofloxacin [CIP] MIC, < 0.125 mg/ liter) and 194 fluoroquinolone- resistant isolates (CIP MIC, > 2 mg/ liter). The MIC50 and MIC90 for TGC in fluoroquinolone- resistant isolates were 2-fold higher than those in fluoroquinolone-susceptible isolates (MIC50, 0.5 mg/liter versus 0.25 mg/liter; MIC90, 1 mg/ liter versus 0.5 mg/ liter, respectively). Two fluoroquinolone-resistant isolates (O25b:H4-ST131-H30R and O125:H37-ST48) were TGC resistant (MICs of 4 and 16 mg/liter, respectively), and four other isolates of O25b:H4-ST131-H30R and an isolate of O1-ST648 showed an intermediate interpretation (MIC, 2 mg/liter). No TGC-resistant/ intermediate strains were found among the fluoroquinolone-susceptible isolates. The TGC- resistant/ intermediate isolates expressed higher levels of acrA and acrB and had lower intracellular TGC concentrations than susceptible isolates, and they possessed mutations in acrR and/or marR. The MICs of acrAB-deficient mutants were markedly lower (0.25 mg/liter) than those of the parental strain. After continuous stepwise exposure to CIP in vitro, six of eight TGC-susceptible isolates had reduced TGC susceptibility. Two of them acquired TGC resistance (TGC MIC, 4 mg/liter) and exhibited expression of acrA and acrB and mutations in acrR and/or marR. In conclusion, a population of fluoroquinolone-resistant E. coli isolates, including major extraintestinal pathogenic lineages O25b: H4-ST131-H30R and O1-ST648, showed reduced susceptibility to TGC due to overexpression of the efflux pump AcrAB- TolC, leading to decreased intracellular concentrations of the antibiotics that may be associated with the development of fluoroquinolone resistance.

DOI

構造情報の蓄積から見えてきたリポテイコ酸の細菌種による構造多様性.

白石宗, 横田伸一, 吹谷智, 横田篤

日本乳酸菌学会誌 28 ( 3 ) 177 - 177 2017 [Invited]

J-GLOBAL

Adaptive Cross-Resistance to Aminoglycoside Antibiotics in Pseudomonas aeruginosa Induced by Topical Dosage of Neomycin

Shuji Uemura, Shin-ichi Yokota, Tsukasa Shiraishi, Manabu Kitagawa, Suguru Hirayama, Ryoko Kyan, Hirotoshi Mizuno, Keigo Sawamoto, Hiroyuki Inoue, Atsushi Miyamoto, Eichi Narimatsu

CHEMOTHERAPY ( KARGER ) 62 ( 2 ) 121 - 127 2017 [Refereed]

Background: Topical antimicrobial formulations containing neomycin are commonly used to prevent and treat burn infections. However, Pseudomonas aeruginosa shows rapid acquisition of adaptive resistance to neomycin. This study aimed to evaluate the survival of P. aeruginosa during exposure to neomycin at high concentrations comparable to those used in topical formulations, and to investigate the effect of adaptive resistance to neomycin on the susceptibility to other aminoglycosides. Methods: Strain IID1130 [neomycin minimal inhibitory concentration (MIC) = 4 mu g/ml] was incubated on an agar medium containing neomycin at high concentrations (8-4,096 mu g/ml), and growing colonies were macroscopically observed. Acquisition of adaptive resistance was examined for 5 P. aeruginosa strains. Cells were sequentially passaged on agar medium containing neomycin with step-wise increased concentrations (82,048 mu g/ml). To assess reversion of antibiotic susceptibility, the resulting colonies were repeatedly subcultured on antibiotic-free agar plates. Results: Growing IID1130 colonies were macroscopically detected on a neomycin-containing ( 2,048 mu g/ml) agar plate for 48 h. These cells showed increasing MIC for not only neomycin, but also gentamicin and amikacin; the MIC values were occasionally higher than the breakpoints. When the adapted cells were subcultured on antibiotic-free agar, several passages were required for reversion of susceptibility. Conclusions: Our findings suggest that P. aeruginosa can survive in the presence of neomycin with a concentration typically used in topical dosage forms, and that the acquired adaptive resistance is persistent and is accompanied by cross-resistance to other aminoglycosides. (C) 2016 S. Karger AG, Basel

DOI

Mechanism of Reduced Susceptibility to Fosfomycin in Escherichia coli Clinical Isolates

Yasuo Ohkoshi, Toyotaka Sato, Yuuki Suzuki, Soh Yamamoto, Tsukasa Shiraishi, Noriko Ogasawara, Shin-ichi Yokota

BIOMED RESEARCH INTERNATIONAL ( HINDAWI LTD ) 2017 5470241 2017 [Refereed]

In recent years, multidrug resistance of Escherichia coli has become a serious problem. However, resistance to fosfomycin (FOM) has been low. We screened E. coli clinical isolates with reduced susceptibility to FOM and characterized molecular mechanisms of resistance and reduced susceptibility of these strains. Ten strains showing reduced FOM susceptibility (MIC >= 8 mu g/mL) in 211 clinical isolates were found and examined. Acquisition of genes encoding FOM-modifying enzyme genes (fos genes) and mutations in murA that underlie high resistance to FOM were not observed. We examined ability of FOM incorporation via glucose-6phosphate (G6P) transporter and sn-glycerol-3-phosphate transporter. In ten strains, nine showed lack of growth on M9 minimum salt agar supplemented with G6P. Eight of the ten strains showed fluctuated induction by G6P of uhpT that encodes G6P transporter expression. Nucleotide sequences of the uhpT, uhpA, glpT, ptsI, and cyaA shared several deletions and amino acid mutations in the nine strains with lack of growth on G6P-supplemented M9 agar. In conclusion, reduction of uhpT function is largely responsible for the reduced sensitivity to FOM in clinical isolates that have not acquired FOM-modifying genes or mutations in murA. However, there are a few strains whose mechanisms of reduced susceptibility to FOM are still unclear.

DOI

家族内発症のCrohn病３家系７症例における臨床的特徴の比較検討ならびに疾患関連遺伝子（TNFSF15）の解析

戸板成昭, 藤原伸一, 高橋美智子, 今野武津子, 横田伸一

臨牀小児医学 65 ( 1-6 ) 11 - 14 2017 [Refereed]

J-GLOBAL

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Papers - YOKOTA Shinichi