Details of a Researcher - YOKOTA Shinichi

Papers - YOKOTA Shinichi

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Rapid and Integrated Bacterial Evolution Analysis unveils gene mutations and clinical risk of Klebsiella pneumoniae.

Kojiro Uemura, Toyotaka Sato, Soh Yamamoto, Noriko Ogasawara, Jirachaya Toyting, Kotaro Aoki, Akira Takasawa, Masayuki Koyama, Atsushi Saito, Takayuki Wada, Kaho Okada, Yurie Yoshida, Koji Kuronuma, Chie Nakajima, Yasuhiko Suzuki, Motohiro Horiuchi, Kenichi Takano, Satoshi Takahashi, Hirofumi Chiba, Shin-Ichi Yokota

Nature communications 16 ( 1 ) 2917 - 2917 2025.03 [International journal]

Bacteria continually evolve. Previous studies have evaluated bacterial evolution in retrospect, but this approach is based on only speculation. Cohort studies are reliable but require a long duration. Additionally, identifying which genetic mutations that have emerged during bacterial evolution possess functions of interest to researchers is an exceptionally challenging task. Here, we establish a Rapid and Integrated Bacterial Evolution Analysis (RIBEA) based on serial passaging experiments using hypermutable strains, whole-genome and transposon-directed sequencing, and in vivo evaluations to monitor bacterial evolution in a cohort for one month. RIBEA reveals bacterial factors contributing to serum and antimicrobial resistance by identifying gene mutations that occurred during evolution in the major respiratory pathogen Klebsiella pneumoniae. RIBEA also enables the evaluation of the risk for the progression and the development of invasive ability from the lung to blood and antimicrobial resistance. Our results demonstrate that RIBEA enables the observation of bacterial evolution and the prediction and identification of clinically relevant high-risk bacterial strains, clarifying the associated pathogenicity and the development of antimicrobial resistance at genetic mutation level.

DOI PubMed

Immunostimulatory activity of lipoteichoic acid with three fatty acid residues derived from Limosilactobacillus antri JCM 15950 T

Shino Yamasaki-Yashiki, Tsukasa Shiraishi, Mai Gyobu, Haruna Sasaki, Jun Kunisawa, Shin-ichi Yokota, Yoshio Katakura

Applied and Environmental Microbiology ( American Society for Microbiology ) 2024.09

ABSTRACT Some strains of lactic acid bacteria can regulate the host’s intestinal immune system. Bacterial cells and membrane vesicles (MVs) of Limosilactobacillus antri JCM 15950 ^T promote immunoglobulin A (IgA) production in murine Peyer’s patch cells via toll-like receptor (TLR) 2. This study aimed to investigate the role of lipoteichoic acid (LTA), a ligand of TLR2, in the immunostimulatory activity of these bacterial cells and their MVs. LTA extracted from bacterial cells was purified through hydrophobic interaction chromatography and then divided into fractions LTA1 and LTA2 through anion-exchange chromatography. LTA1 induced greater interleukin (IL)-6 production from macrophage-like RAW264 cells than LTA2, and the induced IL-6 production was suppressed by TLR2 neutralization using an anti-TLR2 antibody. The LTAs in both fractions contained two hexose residues in the glycolipid anchor; however, LTA1 was particularly rich in triacyl LTA. The free hydroxy groups in the glycerol phosphate (GroP) repeating units were substituted by d -alanine ( d -Ala) and α-glucose in LTA1, but only by α-glucose in LTA2. The dealanylation of LTA1 slightly suppressed IL-6 production in RAW264 cells, whereas deacylation almost completely suppressed IL-6 production. Furthermore, IL-6 production induced by dealanylated LTA1 was markedly higher than that induced by dealanylated LTA2. These results indicated that the critical moieties for the immunostimulatory activity of L. antri -derived LTA were the three fatty acid residues rather than the substitution with d -Ala in GroP. LTA was also detected in MVs, suggesting that the triacyl LTA, but not the diacyl LTA, translocated to the MVs and conferred immunostimulatory activity. IMPORTANCE Some lactic acid bacteria activate the host intestinal immune system via toll-like receptor (TLR) 2. Lipoteichoic acid (LTA) is a TLR2 ligand; however, the moieties of LTA that determine its immunostimulatory activity remain unclear because of the wide diversity of LTA partial structures. We found that Limosilactobacillus antri JCM 15950 ^T has three types of LTAs (triacyl, diacyl, and monoacyl LTAs). Specifically, structural analysis of the LTAs revealed that triacyl LTA plays a crucial role in immunostimulation and that the fatty acid residues are essential for the activity. The three acyl residues are characteristic of LTAs from many lactic acid bacteria, and our findings can explain the immunostimulatory mechanisms widely exhibited by lactic acid bacteria. Furthermore, the immunostimulatory activity of membrane vesicles released by L. antri JCM 15950 ^T is due to the transferred LTA, demonstrating a novel mechanism of membrane vesicle-mediated immunostimulation.

DOI

Development of a natural product optimization strategy for inhibitors against MraY, a promising antibacterial target.

Kazuki Yamamoto, Toyotaka Sato, Aili Hao, Kenta Asao, Rintaro Kaguchi, Shintaro Kusaka, Radhakrishnam Raju Ruddarraju, Daichi Kazamori, Kiki Seo, Satoshi Takahashi, Motohiro Horiuchi, Shin-Ichi Yokota, Seok-Yong Lee, Satoshi Ichikawa

Nature communications 15 ( 1 ) 5085 - 5085 2024.06 [International journal]

MraY (phospho-N-acetylmuramoyl-pentapeptide-transferase) inhibitory natural products are attractive molecules as candidates for a new class of antibacterial agents to combat antimicrobial-resistant bacteria. Structural optimization of these natural products is required to improve their drug-like properties for therapeutic use. However, chemical modifications of these natural products are painstaking tasks due to complex synthetic processes, which is a bottleneck in advancing natural products to the clinic. Here, we develop a strategy for a comprehensive in situ evaluation of the build-up library, which enables us to streamline the preparation of the analogue library and directly assess its biological activities. We apply this approach to a series of MraY inhibitory natural products. Through construction and evaluation of the 686-compound library, we identify promising analogues that exhibit potent and broad-spectrum antibacterial activity against highly drug-resistant strains in vitro as well as in vivo in an acute thigh infection model. Structures of the MraY-analogue complexes reveal distinct interaction patterns, suggesting that these analogues represent MraY inhibitors with unique binding modes. We further demonstrate the generality of our strategy by applying it to tubulin-binding natural products to modulate their tubulin polymerization activities.

DOI PubMed

Traces of pandemic fluoroquinolone-resistant Escherichia coli clone ST131 transmitted from human society to aquatic environments and wildlife in Japan

Toyotaka Sato, Kojiro Uemura, Mitsuru Yasuda, Aiko Maeda, Toshifumi Minamoto, Kazuki Harada, Michiyo Sugiyama, Shiori Ikushima, Shin-ichi Yokota, Motohiro Horiuchi, Satoshi Takahashi, Testuo Asai

One Health ( Elsevier BV ) 18 100715 2024.06 [Refereed]

DOI

The clarithromycin-binding proteins NIPSNAP1 and 2 regulate cytokine production through mitochondrial quality control.

Soh Yamamoto, Noriko Ogasawara, Yukari Mitsuhashi, Kenichi Takano, Shin-Ichi Yokota

Scientific reports 14 ( 1 ) 2354 - 2354 2024.01 [International journal]

The mechanism underlying the anti-inflammatory effect of macrolide antibiotics, such as clarithromycin (CAM), remains to be clarified. The CAM-binding proteins 4-nitrophenylphosphatase domain and non-neuronal synaptosomal associated protein 25 (SNAP25)-like protein homolog (NIPSNAP) 1 and 2 are involved in the immune response and mitochondrial homeostasis. However, the axis between CAM-NIPSNAP-mitochondria and Toll-like receptor (TLR) and their molecular mechanisms remain unknown. In this study, we sought to elucidate the relationship between mitochondrial homeostasis mediated by NIPSNAP1 and 2 and the immunomodulatory effect of CAM. NIPSNAP1 or 2 knockdown (KD) by RNA interference impaired TLR4-mediated interleukin-8 (IL-8) production. Similar impairment was observed upon treatment with mitochondrial function inhibitors. However, IL-8 secretion was not impaired in NIPSNAP1 and 2 individual knockout (KO) and double KO (DKO) cells. Moreover, the oxygen consumption rate (OCR) in mitochondria measured using a flex analyzer was significantly reduced in NIPSNAP1 or 2 KD cells, but not in DKO cells. CAM also dose-dependently reduced the OCR. These results indicate that CAM suppresses the IL-8 production via the mitochondrial quality control regulated by temporary functional inhibition of NIPSNAP1 and 2. Our findings provide new insight into the mechanisms underlying cytokine production, including the TLR-mitochondria axis, and the immunomodulatory effects of macrolides.

DOI PubMed

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]

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

Serotype replacement and an increase in non-encapsulated isolates among community-acquired infections of Streptococcus pneumoniae during post-vaccine era in Japan.

Shin-Ichi Yokota, Naoyuki Tsukamoto, Toyotaka Sato, Yasuo Ohkoshi, Soh Yamamoto, Noriko Ogasawara

IJID regions 8 105 - 110 2023.09 [International journal]

OBJECTIVES: It is feared that the serotype replacement of Streptococcus pneumoniae occurred by the introduction of pneumococcal vaccines as periodical inoculation leads to reduced efficacy of the approved vaccines and altered antimicrobial susceptibility. METHODS: We determined serotypes of 351 S. pneumoniae isolates collected at a commercial clinical laboratory in Hokkaido prefecture, Japan, from December 2018 to February 2019 by using the polymerase chain reaction procedure of the US Centers for Disease Control and Prevention. Antimicrobial susceptibility and resistance gene profiles were also examined. RESULTS: Vaccine coverage rates were 7.9% for 13-valent conjugate vaccine, and 32.5% for 23-valent polysaccharide vaccine, respectively. Non-typable strains were 19.7%. cpsA-positive isolates (group I), and null capsule clade (NCC)1, NCC2 and NCC3 (group II) comprised 31.3%, 28.4%, 32.8%, and 7.5% of the 69 non-typable strains, respectively. No penicillin-resistant/intermediate isolates were found; however, serotypes 35B and 15A/F showed low susceptibility to β-lactams. Only five strains (1.4%) were levofloxacin-resistant, and all were from the older persons, and three strains were serotype 35B. CONCLUSION: The progression of serotype replacement in non-invasive pneumococcal infections has occurred during the post-vaccine era in Japan, and non-encapsulated isolates, such as NCC, have increased. Antimicrobial susceptibility is not worsened.

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]

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

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

Rapid, simple, and cost-effective plaque assay for murine norovirus using microcrystalline cellulose.

Soh Yamamoto, Yuka Sudo-Yokoyama, Noriko Ogasawara, Shin-Ichi Yokota

Journal of virological methods 316 114715 - 114715 2023.06 [International journal]

Murine norovirus (MNV) is used widely as a practical alternative to human norovirus (HuNoV). Plaque-forming assays for MNV are important for developing therapeutic agents against HuNoV infections. Although agarose-overlay MNV assays have been reported, recent improvements in cellulose derivatives suggest that they could be optimized further, particularly with respect to improving the overlay material. To determine which overlay material is optimal for the MNV plaque assay, we compared four typical cellulose derivatives [microcrystalline cellulose (MCC), hydroxyethyl cellulose (HEC), hydroxypropyl methylcellulose (HPMC), and carboxymethyl cellulose (CMC)] with conventional agarose. We found that 3.5% (w/v) MCC-containing medium provided clear round-shaped plaques on RAW 264.7 cells 1 day after inoculation; the visibility of plaques was comparable with that of the original agarose-overlay assay. Removing residual MCC powder from the MCC-overlay assay before fixing was important for obtaining distinct plaques that are clearly countable. Finally, after calculating the plaque diameter as a percentage of well diameter, we found that 12- and 24-well plates were better than other plates for accurate plaque counting. The MCC-based MNV plaque assay is cost-effective and rapid, and produces plaques that are easy to count. Accurate virus quantification using this optimized plaque assay will enable reliable estimation of norovirus titers.

DOI PubMed

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]

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

Corrigendum to 'Clonal/subclonal changes and accumulation of CTX-M-type β-lactamase genes in fluoroquinolone-resistant Escherichia coli ST131 and ST1193 strains isolated during the past 12 years, Japan' [Journal of Global Antimicrobial Resistance 27 (2021) 150-155].

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

Journal of global antimicrobial resistance 32 195 - 195 2023.03 [International journal]

DOI PubMed

Candida albicansは尿糖の存在下で増殖促進に加えてアゾール系やフルシトシンの抗真菌薬の感受性が低下する

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 ) 71 ( 2 ) 175 - 175 2023.03

Klebsiella pneumoniaeにおける遺伝子変異頻度と病原性の関連性評価

上村幸二朗, 佐藤豊孝, 黒沼幸治, 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 ) 71 ( 2 ) 179 - 179 2023.03

抗菌性物質・薬剤耐性/生体防御大腸菌ST131におけるmcr-1保有プラスミドの獲得による病原性減弱機構(Antimicrobial agents and resistance/Host defense Virulent attenuation mechanism by acquisition of mcr-1-harboring plasmid into Escherichia coli ST131)

佐藤豊孝, 山本聡, 小笠原徳子, 臼井優, 長野則之, 土井洋平, 堀内基広, 高橋聡, 横田伸一, 田村豊

日本細菌学雑誌 ( 日本細菌学会 ) 78 ( 1 ) 48 - 48 2023.02

Discovery of Biologically Optimized Polymyxin Derivatives Facilitated by Peptide Scanning and In Situ Screening Chemistry

Rintaro Kaguchi, Akira Katsuyama, Toyotaka Sato, Satoshi Takahashi, Motohiro Horiuchi, Shin-ichi Yokota, Satoshi Ichikawa

Journal of the American Chemical Society ( American Chemical Society (ACS) ) 2023.01 [Refereed]

DOI

Human pathogenic bacteria on high-touch dry surfaces can be controlled by warming to human-skin temperature under moderate humidity.

Ayano Konno, Torahiko Okubo, Yoshiaki Enoeda, Tomoko Uno, Toyotaka Sato, Shin-Ichi Yokota, Rika Yano, Hiroyuki Yamaguchi

PloS one 18 ( 9 ) e0291765 2023 [Refereed] [International journal]

Healthcare-associated infections have become a major health issue worldwide. One route of transmission of pathogenic bacteria is through contact with "high-touch" dry surfaces, such as handrails. Regular cleaning of surfaces with disinfectant chemicals is insufficient against pathogenic bacteria and alternative control methods are therefore required. We previously showed that warming to human-skin temperature affected the survival of pathogenic bacteria on dry surfaces, but humidity was not considered in that study. Here, we investigated environmental factors that affect the number of live bacteria on dry surfaces in hospitals by principal component analysis of previously-collected data (n = 576, for CFU counts), and experimentally verified the effect of warming to human-skin temperature on the survival of pathogenic bacteria on dry surfaces under humidity control. The results revealed that PCA divided hospital dry surfaces into four groups (Group 1~4) and hospital dry surfaces at low temperature and low humidity (Group 3) had much higher bacterial counts as compared to the others (Group 1 and 4) (p<0.05). Experimentally, warming to human-skin temperature (37°C with 90% humidity) for 18~72h significantly suppressed the survival of pathogenic bacteria on dry surfaces, such as plastic surfaces [p<0.05 vs. 15°C (Escherichia coli DH5α, Staphylococcus aureus, Pseudomonas aeruginosa, Acinetobacter baumannii, and blaNDM-5 E. coli)] or handrails [p<0.05 vs. 15~25°C (E. coli DH5α, S. aureus, P. aeruginosa, A. baumannii)], under moderate 55% humidity. Furthermore, intermittent heating to human-skin temperature reduced the survival of spore-forming bacteria (Bacillus subtilis) (p<0.01 vs. continuous heating to human-skin temperature). NhaA, an Na+/H+ antiporter, was found to regulate the survival of bacteria on dry surfaces, and the inhibitor 2-aminoperimidine enhanced the effect of warming at human-skin temperature on the survival of pathogenic bacteria (E. coli DH5α, S. aureus, A. baumannii) on dry surfaces. Thus, warming to human-skin temperature under moderate humidity is a useful method for impairing live pathogenic bacteria on high-touch surfaces, thereby helping to prevent the spread of healthcare-associated infections.

DOI PubMed

Synthesis of macrocyclic nucleoside antibacterials and their interactions with MraY.

Takeshi Nakaya, Miyuki Yabe, Ellene H Mashalidis, Toyotaka Sato, Kazuki Yamamoto, Yuta Hikiji, Akira Katsuyama, Motoko Shinohara, Yusuke Minato, Satoshi Takahashi, Motohiro Horiuchi, Shin-Ichi Yokota, Seok-Yong Lee, Satoshi Ichikawa

Nature communications 13 ( 1 ) 7575 - 7575 2022.12 [International journal]

The development of new antibacterial drugs with different mechanisms of action is urgently needed to address antimicrobial resistance. MraY is an essential membrane enzyme required for bacterial cell wall synthesis. Sphaerimicins are naturally occurring macrocyclic nucleoside inhibitors of MraY and are considered a promising target in antibacterial discovery. However, developing sphaerimicins as antibacterials has been challenging due to their complex macrocyclic structures. In this study, we construct their characteristic macrocyclic skeleton via two key reactions. Having then determined the structure of a sphaerimicin analogue bound to MraY, we use a structure-guided approach to design simplified sphaerimicin analogues. These analogues retain potency against MraY and exhibit potent antibacterial activity against Gram-positive bacteria, including clinically isolated drug resistant strains of S. aureus and E. faecium. Our study combines synthetic chemistry, structural biology, and microbiology to provide a platform for the development of MraY inhibitors as antibacterials against drug-resistant bacteria.

DOI PubMed

One Health Approachに基づいたフルオロキノロン耐性大腸菌の市中内拡散・定着様式の解明

佐藤豊孝, 立花徹, 玉井聡, 星野祐治, 鳥越慎吾, 榊原啓一郎, 前谷茂樹, 福田昭, 大久保寅彦, 臼井優, 高橋聡, 横田伸一, 田村豊, 堀内基広

日本獣医学会学術集会講演要旨集 ( (公社)日本獣医学会 ) 165回 [F2A - 10] 2022.09

COVID-19における嗅裂閉鎖所見と嗅覚障害の検討

山本圭佑, 藤谷好弘, 山直也, 黒沼幸治, 小笠原徳子, 横田伸一, 高橋聡, 高野賢一

日本耳鼻咽喉科免疫アレルギー感染症学会誌 ( 日本耳鼻咽喉科免疫アレルギー感染症学会 ) 2 ( 2 ) 49 - 54 2022.06

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Papers - YOKOTA Shinichi