Papers - YOKOTA Shinichi

環境からヒトの生活に侵入する病原微生物 家庭内One-Health 伴侶動物由来耐性菌と人臨床検体由来耐性菌の比較

佐藤 豊孝, 高橋 聡, 横田 伸一, 田村 豊

日本化学療法学会雑誌 ( (公社)日本化学療法学会 )  69 ( 1 ) 50 - 50  2021.01

環境からヒトの生活に侵入する病原微生物 家庭内One-Health 伴侶動物由来耐性菌と人臨床検体由来耐性菌の比較

佐藤 豊孝, 高橋 聡, 横田 伸一, 田村 豊

日本化学療法学会雑誌 ( (公社)日本化学療法学会 )  69 ( 1 ) 50 - 50  2021.01

生体内菌発育必須因子(vivoEF)を標的した血流感染症特異的vivoEF阻害薬の感染部位特異的抗菌活性効果の検討

佐藤 豊孝, 臼井 優, 高橋 聡, 横田 伸一

日本化学療法学会雑誌 ( (公社)日本化学療法学会 )  69 ( 1 ) 90 - 90  2021.01

生体内菌発育必須因子(vivoEF)を標的した血流感染症特異的vivoEF阻害薬の感染部位特異的抗菌活性効果の検討

佐藤 豊孝, 臼井 優, 高橋 聡, 横田 伸一

日本化学療法学会雑誌 ( (公社)日本化学療法学会 )  69 ( 1 ) 90 - 90  2021.01

Emergence of the Novel Aminoglycoside Acetyltransferase Variant aac(6′)-Ib-D179Y and Acquisition of Colistin Heteroresistance in Carbapenem-Resistant Klebsiella pneumoniae Due to a Disrupting Mutation in the DNA Repair Enzyme MutS

Toyotaka Sato, Takayuki Wada, Suguru Nishijima, Yukari Fukushima, Chie Nakajima, Yasuhiko Suzuki, Satoshi Takahashi, Shin-ichi Yokota

mBio ( American Society for Microbiology )  11 ( 6 )  2020.12

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The emergence of multidrug resistance in pathogens such as Klebsiella pneumoniae is of great clinical concern. Antimicrobial resistance sometimes arises during the course of an infection.

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Sitafloxacin has a potent activity for eradication of extended spectrum β-lactamase-producing fluoroquinolone-resistant Escherichia coli forming intracellular bacterial communities in uroepithelial cells.

Yoshiki Hiyama, Toyotaka Sato, Satoshi Takahashi, Soh Yamamoto, Yukari Fukushima, Chie Nakajima, Yasuhiko Suzuki, Shin-Ichi Yokota, Naoya Masumori

Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy   26 ( 12 ) 1272 - 1277  2020.12  [International journal]

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INTRODUCTION: Eradication of asymptomatic bacteriuria (ASB) before urological procedures is important to reduce the risk for infectious complications after surgery. However, the appropriate regimen for antimicrobial treatment has not been fully determined. We experienced continuous (over 10 months) isolation of extended spectrum β-lactamase (ESBL)-producing fluoroquinolone-resistant Escherichia coli from urine of an asymptomatic patient. The four isolates obtained (SMESC1 to 4) were international high-risk clones of O25b:H4-ST131-H30R, and originated from one strain, as revealed by the whole genome sequences. Although the patient received meropenem (MEPM) and fosfomycin (FOM), to which the strains were susceptible before the urological procedures, they could not be eradicated. METHODS: To explore the reason for the continuous isolation even after MEPM and FOM administration, antimicrobial killing of adherent and/or intracellular bacterial communities (IBC) formed by coculture of the E. coli cells and T24 bladder epithelial cells were examined. RESULTS: FOM and levofloxacin did not decrease viable E. coli cells compared with gentamicin. MEPM partly decreased them, and sitafloxacin (STFX) decreased them most potently. These observations indicate that E. coli can survive in the urinary tract under antimicrobial administration, and some antimicrobials such as FOM and MEPM cannot eradicate E. coli in uroepithelial cells. Adhesion on urinary epithelial cells and/or IBC formation might result in continuous isolation from the urinary tract and recurrence of ASB and urinary tract infections. CONCLUSIONS: The present study suggests that STFX is a promising optional agent for the eradication of ESBL-producing fluoroquinolone-resistant E. coli in the urinary tract before urological procedures.

DOI PubMed

Whole-Genome Sequence of Fluoroquinolone-Resistant Escherichia coli HUE1, Isolated in Hokkaido, Japan.

Montgomery Munby, Jumpei Fujiki, Kotaro Aoki, Chika Kawaguchi, Keisuke Nakamura, Tomohiro Nakamura, Michihito Sasaki, Toyotaka Sato, Masaru Usui, Hirofumi Sawa, Shin-Ichi Yokota, Yutaka Tamura, Hidetomo Iwano

Microbiology resource announcements   9 ( 46 )  2020.11  [International journal]

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We report the complete genome sequence of Escherichia coli strain HUE1, isolated from the urinary catheter of a female patient, showing fluoroquinolone resistance without quinolone resistance-determining region mutations. To facilitate the exploration of the molecular characteristics of HUE1, the whole genome was sequenced using long- and short-read platforms.

DOI PubMed

Elucidating the Structural Requirement of Uridylpeptide Antibiotics for Antibacterial Activity.

Yuma Terasawa, Chisato Sataka, Toyotaka Sato, Kazuki Yamamoto, Yukari Fukushima, Chie Nakajima, Yasuhiko Suzuki, Akira Katsuyama, Takanori Matsumaru, Fumika Yakushiji, Shin-Ichi Yokota, Satoshi Ichikawa

Journal of medicinal chemistry   63 ( 17 ) 9803 - 9827  2020.09  [International journal]

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The synthesis and biological evaluation of analogues of uridylpeptide antibiotics were described, and the molecular interaction between the 3'-hydroxy analogue of mureidomycin A (3'-hydroxymureidomycin A) and its target enzyme, phospho-MurNAc-pentapeptide transferase (MraY), was analyzed in detail. The structure-activity relationship (SAR) involving MraY inhibition suggests that the side chain at the urea-dipeptide moiety does not affect the MraY inhibition. However, the anti-Pseudomonas aeruginosa activity is in great contrast and the urea-dipeptide motif is a key contributor. It is also suggested that the nucleoside peptide permease NppA1A2BCD is responsible for the transport of 3'-hydroxymureidomycin A into the cytoplasm. A systematic SAR analysis of the urea-dipeptide moiety of 3'-hydroxymureidomycin A was further conducted and the antibacterial activity was determined. This study provides a guide for the rational design of analogues based on uridylpeptide antibiotics.

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Emergence of vancomycin- and teicoplanin-resistant Enterococcus faecium via vanD5-harbouring large genomic island.

Toyotaka Sato, Takayuki Wada, Masaaki Shinagawa, Yukari Fukushima, Chie Nakajima, Yasuhiko Suzuki, Satoshi Takahashi, Shin-Ichi Yokota

The Journal of antimicrobial chemotherapy    2020.06  [Refereed]  [International journal]

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BACKGROUND: Treatment of VRE is of clinical concern. While certain numbers of vanD-type VRE have been isolated, only two vanD5-harbouring Enterococcus faecium isolates have been reported in Canada and Japan. METHODS: We report the isolation of vanD5-type E. faecium and the first ever determination of the whole-genome sequence to investigate the possible mechanisms of the acquisition of the vanD5 gene cluster in E. faecium. RESULTS: Two vanD5-harbouring vancomycin-resistant E. faecium were isolated from the skin (SMVRE19) and faeces (SMVRE20) of a patient with a skin ulcer in Japan. The isolates exhibited vancomycin and teicoplanin MIC values of 128 mg/L, whilst the previous isolates of vanD5-harbouring E. faecium were only resistant to vancomycin. SMVRE19 and SMVRE20 were clones related to ST18, which is also seen in vanA- and vanB-type VRE. These isolates harboured an insertion element, ISEfm1, in the ddl gene, similar to a previously described teicoplanin-resistant vanD3-type E. faecium. The vanD5 gene cluster was integrated into the SMVRE20 chromosome as a part of a large genomic island (approximately 127 kb), similar to other recently spreading vanD variants in the Netherlands. The genomic island shared the greatest similarity with a part of the Blautia coccoides genome sequence, except for the region surrounding the vanD gene cluster. CONCLUSIONS: This study reports that emergence of vancomycin- and teicoplanin-resistant vanD5-type E. faecium occurred via acquisition of the vanD5 cluster and ISEfm1 insertion into ddl. Considering the genetic similarity between the various VRE strains, the current study should serve as a warning against the spread of vanD5-type VRE.

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Fosfomycinによる術前除菌が無効であった尿道損傷患者の尿から検出されたESBL産生大腸菌の細菌学的検討

桧山 佳樹, 佐藤 豊孝, 高橋 聡, 舛森 直哉, 横田 伸一

日本化学療法学会雑誌 ( (公社)日本化学療法学会 )  68 ( 3 ) 451 - 451  2020.05

Campylobacter upsaliensis isolated from a giant hepatic cyst.

Yasuo Ohkoshi, Toyotaka Sato, Hiromi Murabayashi, Kohei Sakai, Yasunari Takakuwa, Yukari Fukushima, Chie Nakajima, Yasuhiko Suzuki, Shin-Ichi Yokota

Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy    2020.03  [Refereed]  [International journal]

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Campylobacter upsaliensis is an enteropathogenic bacterium in animals, and is also rarely isolated from humans, where it can cause enteritis and bacteremia. This report describes the first case of isolation of C. upsaliensis from an infected giant hepatic cyst. This bacterium could not be cultured from abscess punctuate in a usual Campylobacter-selection medium (charcoal cefoperazone deoxycholate agar medium), because of high concentration of cefoperazone as a selection agent. It could not identified by matrix-assisted laser desorption ionization-time of flight mass spectrum. Rather, it was identified as C. upsaliensis by whole genome sequencing, including by multilocus sequence typing.

DOI PubMed

院内感染 病院から病院外へ 病院外から病院へ 伴侶動物領域におけるESBL産生菌の現状

佐藤 豊孝, 田村 豊, 高橋 聡, 横田 伸一

日本化学療法学会雑誌 ( (公社)日本化学療法学会 )  68 ( 2 ) 249 - 250  2020.03

プラスミド性コリスチン耐性菌はヒトの健康に対するハザードか? mcr保有プラスミドが大腸菌の性状に及ぼす影響とゲノム解析

臼井 優, 福田 昭, 鈴木 仁人, 矢原 耕史, 川西 路子, 佐藤 豊孝, 横田 伸一, 高橋 聡, 浅井 鉄夫, 田村 豊

感染症学雑誌 ( (一社)日本感染症学会 )  94 ( 臨増 ) 232 - 232  2020.03

Haemophilus influenzaeのキノロン系抗菌薬耐性に関与する遺伝子変異の解析

本田 宏幸, 佐藤 豊孝, 黒沼 幸治, 高橋 聡, 高橋 弘毅, 横田 伸一

感染症学雑誌 ( (一社)日本感染症学会 )  94 ( 臨増 ) 317 - 317  2020.03

伴侶動物領域におけるESBL産生菌の現状

佐藤 豊孝, 田村 豊, 高橋 聡, 横田 伸一

感染症学雑誌 ( (一社)日本感染症学会 )  94 ( 2 ) 223 - 223  2020.03

プラスミド性コリスチン耐性菌はヒトの健康に対するハザードか? コリスチン耐性菌の定着性と治療効果に及ぼす影響

佐藤 豊孝, 小笠原 徳子, 臼井 優, 鈴木 仁人, 長野 則之, 土井 洋平, 田村 豊, 高橋 聡, 横田 伸一

感染症学雑誌 ( (一社)日本感染症学会 )  94 ( 臨増 ) 232 - 233  2020.03

なるほど微生物学講座-不思議なミクロの世界- インフルエンザ菌におけるβ-ラクタムおよびキノロン系抗菌薬耐性に関する分子遺伝学的解析

佐藤 豊孝, 本田 宏幸, 黒沼 幸治, 高橋 聡, 横田 伸一

感染症学雑誌 ( (一社)日本感染症学会 )  94 ( 臨増 ) 142 - 142  2020.03

生体内菌発育必須因子(vivoEF)を標的とする感染部位特異的(ピンポイント)抗菌薬のスクリーニング

佐藤 豊孝, 小笠原 徳子, 霧島 正浩, 高橋 聡, 横田 伸一

感染症学雑誌 ( (一社)日本感染症学会 )  94 ( 2 ) 248 - 248  2020.03

Contribution of β-lactamase and efflux pump overproduction to tazobactam-piperacillin resistance in clinical isolates of Escherichia coli.

Yuuki Suzuki, Toyotaka Sato, Yukari Fukushima, Chie Nakajima, Yasuhiko Suzuki, Satoshi Takahashi, Shin-Ichi Yokota

International journal of antimicrobial agents     105919 - 105919  2020.02  [Refereed]  [International journal]

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INTRODUCTION: Tazobactam-piperacillin (TZP) is a mixture of a broad-spectrum penicillin and an irreversible β-lactamase inhibitor. TZP is effective against Gram-negative bacteria that produce extended-spectrum β-lactamases, and it is used as a first-line or second-line drug to treat serious infections. METHODS: This study identified three TZP-resistant and two TZP-intermediate strains among 514 clinical isolates of Escherichia coli. RESULTS: These five isolates possessed one or more β-lactamase genes, blaTEM-1, blaCTX-M-2, blaCTX-M-14, and/or blaCMY-8. The expression levels of β-lactamase genes and acrAB genes in the strains were examined by using real-time reverse transcription PCR. The total enzymatic piperacillin-degrading activity in cells was determined. Two TZP-resistance mechanisms were identified: hyperproduction of TEM-1 in the two resistant strains; and simultaneous high production of β-lactamase and efflux pump AcrAB in the two TZP-intermediate isolates. The latter are an international high-risk clone O25b:H4-ST131-H30R. CONCLUSION: TZP resistance is still rare in clinical isolates of E. coli. However, resistance can develop on high production and/or combinations of known antimicrobial resistance mechanisms in different ways.

DOI PubMed

In Vitro Derivation of Fluoroquinolone-Resistant Mutants from Multiple Lineages of Haemophilus influenzae and Identification of Mutations Associated with Fluoroquinolone Resistance.

Hiroyuki Honda, Toyotaka Sato, Masaaki Shinagawa, Yukari Fukushima, Chie Nakajima, Yasuhiko Suzuki, Koji Kuronuma, Satoshi Takahashi, Hiroki Takahashi, Shin-Ichi Yokota

Antimicrobial agents and chemotherapy   64 ( 2 )  2020.01  [Refereed]  [International journal]

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Haemophilus influenzae is a pathogenic bacterium that causes respiratory and otolaryngological infections. The increasing prevalence of β-lactamase-negative high-level ampicillin-resistant H. influenzae (high-BLNAR) is a clinical concern. Fluoroquinolones are alternative agents to β-lactams. However, the emergence and increasing prevalence of fluoroquinolone-resistant H. influenzae have been reported. The current risk of fluoroquinolone resistance in H. influenzae (especially in high-BLNAR) has not yet been evaluated. Here, we examined the development of fluoroquinolone resistance in fluoroquinolone-susceptible clinical H. influenzae isolates in vitro during passaging in the presence of moxifloxacin (from 0.03 to 128 mg/liter). Twenty-nine isolates were examined. Seventeen isolates (58.6%) showed reduced moxifloxacin susceptibility, and 10 of these 17 isolates (34.5% of all isolates) exceeded the Clinical and Laboratory Standards Institute breakpoint for moxifloxacin (MIC of >1 mg/liter) after repeat cultivation on moxifloxacin-containing agar. Seven of these ten isolates were high-BLNAR and represented multiple lineages. We identified 56 novel mutations in 45 genes induced during the development of fluoroquinolone resistance, except the defined quinolone resistance-determining regions (Ser84Leu and Asp88Tyr/Gly/Asn in GyrA and Gly82Asp, Ser84Arg, and Glu88Lys in ParC). Glu153Leu and ΔGlu606 in GyrA, Ser467Tyr and Glu469Asp in GyrB, and ompP2 mutations were novel mutations contributing to fluoroquinolone resistance in H. influenzae In conclusion, H. influenzae clinical isolates from multiple lineages can acquire fluoroquinolone resistance by multiple novel mutations. The higher rate of derivation of fluoroquinolone-resistant H. influenzae from high-BLNAR than β-lactamase-negative ampicillin-susceptible isolates (P = 0.01) raises the possibility of the emergence and spread of fluoroquinolone-resistant high-BLNAR in the clinical setting.

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