Education 【 display / non-display 】

Education 【 display / non-display 】

• 1985

  -

  1987

  北海道大学大学院   理学研究科   化学専攻  

• 1981

  -

  1985

  Hokkaido University   Faculty of Science   Department of Chemistry  

Degree 【 display / non-display 】

Degree 【 display / non-display 】

• 1991.05   The University of Tokyo   Ph.D. (Pharmaceutical Science)

• 1987.04   Hokkaido University   M.Sc

Research Experience 【 display / non-display 】

Research Experience 【 display / non-display 】

• 2025.04

  -

  Now

  Sapporo Medical University   School of Medicine, Dept.of infectious Diseases, Div. of Microbiology   Professor

• 2013.09

  -

  2025.03

  Sapporo Medical University   School of Medicine, Dept.of Microbiology   教授

• 2007.04

  -

  2013.08

  Sapporo Medical University   School of Medicine, Dept.of Microbiology   准教授

  准教授

• 2004.02

  -

  2007.03

  Sapporo Medical University   School of Medicine, Dept.of Microbiology   助教授

  助教授

• 2000.05

  -

  2004.01

  Sapporo Medical University   School of Medicine, Dept.of Microbiology   講師

  講師

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Professional Memberships 【 display / non-display 】

Professional Memberships 【 display / non-display 】

• 　

  　

  　

  日本生化学会

• 　

  　

  　

  JAPANESE SOCIETY OF CHEMOTHERAPY

• 　

  　

  　

  米国微生物学会

• 　

  　

  　

  日本感染症学会

• 　

  　

  　

  臨床ストレス応答学会

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Research Areas 【 display / non-display 】

Research Areas 【 display / non-display 】

• Life sciences   Immunology  

• Life sciences   Virology  

• Life sciences   Bacteriology  

Affiliation 【 display / non-display 】

Affiliation 【 display / non-display 】

• Sapporo Medical University   School of Medicine, Dept.of Infectious Diseases, Div. of Microbiology   Professor  

Papers 【 display / non-display 】

Papers 【 display / non-display 】

• A unique tetrasaccharide-containing anchor glycolipid of lipoteichoic acid is commonly found in Lactobacillus gasseri and Lactobacillus paragasseri.

  Tsukasa Shiraishi, Ryosuke Kutomi, Yamaha Sato, Akihito Endo, Satoru Fukiya, Satoshi Takahashi, Atsushi Yokota, Shin-Ichi Yokota

  Bioscience, biotechnology, and biochemistry    2025.06  [International journal]

  　View Summary

  Lipoteichoic acid (LTA) is a cell surface molecule with physiologically important roles in Gram-positive bacteria. Previously, we identified a novel tetrasaccharide-containing anchor glycolipid in the Lactobacillus gasseri JCM 1131T LTA. However, it is unclear whether this tetrasaccharide-containing anchor glycolipid structure is characteristic of JCM 1131T alone or is commonly found in other L. gasseri-related isolates. Lactobacillus paragasseri has been proposed as a new species, separated from the L. gasseri. In the present study, we characterized chemical structures of LTA from two strains of L. gasseri and four strains of L. paragasseri. All six strains shared a polymer comprising repeating units of glycerophosphate with partial D-alanine substitutions, as well as L. gasseri JCM 1131T. Anchor glycolipid structure suggested that all strains shared a tetrasaccharide-containing glyceroglycolipid with two and three acyl groups. Focusing on LTA from L. gasseri and L. paragasseri species, a tetrasaccharide-containing anchor glycolipid is a specific feature.

  DOI PubMed

• Efficacy of disinfectants and endotoxin-retentive filters for the removal of bacterial DNA from dialysates

  Minoru Nakamura, Ami Murata, Toru Yokoyama, Daisuke Furuya, Tomokazu Indo, Shin-ichi Yokota

  Renal Replacement Therapy ( Springer Science and Business Media LLC )  11 ( 1 )  2025.05

  　View Summary

  Abstract Background Bacterial DNA (bDNA) fragments in dialysate lines can trigger inflammatory responses in patients on dialysis. However, no studies have reported the removal and inactivation of bDNA in dialysate lines using cleaning and disinfection, and management procedures to control bDNA contamination have yet to be established. Methods The efficiency of an endotoxin-retentive filter (ETRF) for the removal of bDNA was examined using an experimental dialysate line incorporating an ETRF and the solubilized materials derived from hot-water-disinfected Pseudomonas aeruginosa cells. To examine the inactivation of bDNA by disinfection, P. aeruginosa cell suspensions were disinfected with hot water, peracetic acid, or sodium hypochlorite, and the amount of bDNA remaining after the disinfection treatment was determined. Single-stranded and double-stranded bDNA were measured using Qubit® fluorometry. The molecular size of bDNA was analyzed by polyacrylamide gel electrophoresis. Results In the spike-and-recovery test of solubilized materials derived from hot-water-disinfected bacterial cells, bDNA leakage was observed when the circuit pressure of the inlet ETRF was elevated. bDNA was inactivated more during disinfection with sodium hypochlorite than with peracetic acid and hot water. Conclusions In addition to the ETRF, disinfection with sodium hypochlorite is an effective method for the management of bDNA in dialysates.

  DOI

• 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]

  　View Summary

  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

• Chemical structure of lipoteichoic acid in the probiotic strain Latilactobacillus curvatus CP2998.

  Tsukasa Shiraishi, Ryo Katsuki, Hiroyuki Kumeta, Shinji Sakata, Shin-Ichi Yokota

  FEMS microbiology letters   372  2025.01  [International journal]

  　View Summary

  Latilactobacillus curvatus, found in various fermented foods, is a promising probiotic with unique health benefits. Lipoteichoic acid (LTA) is a characteristic amphiphilic surface polymer of Gram-positive bacteria and exhibits immunomodulatory activities. Despite the structural diversity of LTA among different bacterial species and strains, no information is available on the chemical structure of LTA in L. curvatus. In this study, we aimed to determine the structure of LTA isolated from L. curvatus CP2998. One- and two-dimensional nuclear magnetic resonance spectra of intact LTA revealed that LTA had a glycerolphosphate polymer as a hydrophilic main chain with partial substitutions of α-linked glucose and d-alanine at the hydroxy group at position 2 of the glycerol residue. The anchor glycolipid fraction was obtained by hydrofluoric acid treatment. Matrix-assisted laser desorption ionization-time-of-flight mass spectrometry spectrum of the anchor glycolipid revealed that it contained diglucosyldiacylglycerol and diglucosylmonoacylglycerol. Our results suggest that L. curvatus CP2998 possesses a typical type I LTA structure; however, the lactic acid bacteria-specific anchor glycolipid structures, such as tri- or tetra-saccharides and three fatty acid residues, were not identified.

  DOI PubMed

• Immunostimulatory activity of lipoteichoic acid with three fatty acid residues derived from <i>Limosilactobacillus antri</i> 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

  　View Summary

  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

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Books and Other Publications 【 display / non-display 】

Books and Other Publications 【 display / non-display 】

• 標準微生物学

  錫谷, 達夫, 松本, 哲哉( Part： Contributor, エンドトキシン（リポ多糖）)

  医学書院  2024.02 ISBN: 9784260053440

• 図解微生物学・感染症・化学療法

  藤井, 暢弘, 山本, 友子( Part： Contributor, 感染症と生体防御，化学療法（抗菌薬）)

  南山堂  2020.10 ISBN: 9784525751326

• エース薬理学

  安西, 尚彦, 安藤, 仁, 浅井, 聡, 金井, 好克( Part： Contributor, 抗菌薬)

  南山堂  2020.08 ISBN: 9784525140717

• シンプル微生物学（改訂第6版）

  横田伸一( Part： Contributor, らせん菌群)

  南江堂  2018

• 病原微生物学 : 基礎と臨床

  荒川, 宜親, 神谷, 茂, 柳, 雄介( Part： Contributor, グラム陰性好気性桿菌)

  東京化学同人  2014.12 ISBN: 9784807908271

Misc 【 display / non-display 】

Misc 【 display / non-display 】

• Lascufloxacin:ディスク拡散法の精度管理限界値と臨床的ブレイクポイントの設定

  荒岡秀樹, 横田伸一, 青木弘太郎, 石井良和, 加地大樹, 黒川正美, 佐々木雅一, 菅井基行, 田中香お里, 中村彰宏, 御手洗聡, 山本剛, 米谷正太

  日本化学療法学会雑誌   73 ( 2 )  2025

  J-GLOBAL

• 薬剤耐性菌感染症における感染部位特異的治療法の可能性評価

  佐藤 豊孝, 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 )  72 ( 1 ) 114 - 114  2024.01

• 薬剤耐性菌感染症における感染部位特異的治療法の可能性評価

  佐藤 豊孝, 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 )  72 ( 1 ) 114 - 114  2024.01

  J-GLOBAL

• 緑膿菌感染症に対する抗体療法の可能性を再考する

  横田伸一

  緑膿菌感染症研究会プログラム・抄録集   58th  2024

  J-GLOBAL

• 金属腐食の有無が熱水消毒前後での生菌数およびエンドトキシン活性値に与える影響

  大友玲奈, 中村実, 清水久恵, 古谷大輔, 印藤智一, 横田伸一

  日本生体医工学会大会プログラム・抄録集(Web)   63rd  2024

  J-GLOBAL

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Awards 【 display / non-display 】

Awards 【 display / non-display 】

• Akiyama Life Science Foundation Award

  2025.09   The Akiyama Life Science Foundation  

• 研究奨励賞

  2017.07   マクロライド新作用研究会  

  Winner： 横田 伸一

• The Rokuzo Kobayashi Memorial Helicobacter Prize

  2009.06   Japanese Society of Helicobacter Research  

  Winner： 横田 伸一

• 研究助成

  2008.10   黒住医学研究振興財団  

  Winner： 横田 伸一

• Scholarship Grant for Research in Basic Medical Sciences and Medical Care

  2005   The Ichiro Kanehara Foundation  

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Research Projects 【 display / non-display 】

Research Projects 【 display / non-display 】

• Apilactobacillus kosoi 10HT 乳酸菌株由来新奇リポテイコ酸の構造および免疫賦活活性の構造活性相関の解明

  Project Year :

  2023.04

  -

  2025.03

   

  横田伸一, 白石宗

• Cell signiling pathway of Toll-like receptor agonists with low activity

  Grant-in-Aid for Scientific Research (B)

  Project Year :

  2020.04

  -

  2023.03

   

  横田 伸一, 小笠原 徳子, 山本 聡, 白石 宗, 永島 裕之, 佐藤 豊孝

  　View Summary

  グラム陽性菌リポテイコ酸（LTA）のIL-8産生誘導能に関して、ヒト結腸癌由来細胞であるCaco-2細胞は、TLR4アゴニストのリポ多糖（LPS）、TLR2/TLR1アゴニストのPam3CSKや３種の乳酸菌LTAにはほとんど応答しないのに対して、黄色ブドウ菌LTAとTLR2/TLR6アゴニストでのみIL-8産生が認められるという特異なサイトカイン応答を示した。検討した3種の乳酸菌LTAと黄色ブドウ球菌LTAの親水性領域はD-アラニン置換のあるグリセロールリン酸ポリマーで共通している。一方、アンカー糖脂質の脂質成分として、黄色ブドウ球菌ではC18:0と分岐脂肪酸であるanteiso-C17:0、anteiso-C15:0から構成され、乳酸菌では不飽和脂肪酸C18:1(n-9)とC16:0、さらにガセリ菌以外ではシクロプロパン環を有するC19:cyが含まれていた。脂質の組成の違いがLTAのCaco-2細胞によるLTAの認識に違いを与えていることが示唆された。 低活性TLRアゴニストの情報伝達とマクロライド系抗菌薬が持つ免疫調節活性の情報伝達系の関連性に関して、クラリスロマイシン結合タンパク質として同定していたNIP-SNAP-1, 2のCrispr-Cas9によるノックアウト（KO）細胞株とsiRNAによるノックダウン（KD）細胞株を作製した。グラム陰性菌リポ多糖（LPS）刺激によるIL-8, IL-6産生誘導は、KDで著明に低下したが、KOでは変化が認められなく、挙動に違いが認められた。NIP-SNAP-1, 2のサイトカイン誘導との関連は示唆されたが、KOにおける挙動では何らかのサルベージ経路が働いているとの仮説を立て、RNseq解析を行い、それに関わる因子の同定に着手した

• 遊離脂肪酸の病原細菌への効果の解明と熱傷局所療法への応用の研究

  基盤研究(C)

  Project Year :

  2017.04

  -

  2023.03

   

  上村 修二, 横田 伸一, 文屋 尚史, 白石 宗

  　View Summary

  黄色ブドウ球菌3株(標準株、市中感染型MRSA、病院感染型MRSA)に対する以下の8種類の脂肪酸：C14:1(cis-9)、C16:0、C16:1(cis-9)、C16:1(trans-9)、C18:0、C18:1(cis-9)、C18:2(cis-9、12)、C20:1(cis-11)のMICを測定した。 脂肪酸単独による検証ではC14:1(cis-9)、C16:1(cis-9)で抗菌活性を認めた。Gentamicin併用ではC14:1(cis-9)、C16:1(cis-9)、C16:1(trans-9)、C18:2(cis-9,12)で増強作用を認めた。Fradiomycin併用ではC14:1(cis-9)、C16:1(cis-9)、C16:1(trans-9)、C18:2(cis-9,12)で増強作用を認めた。Sulfadiazine silver併用では増強作用を認めた脂肪酸はなかった。 本研究でC14:1(cis-9)、C16:1(cis-9)は単独での抗菌活性に加えて、アミノグリコシド系への増強効果も期待できることがわかった。GentamicinとFradiomycinは通常臨床で使用している軟膏に含有されている抗生剤であるため、適切な脂肪酸を加えることで更に抗菌作用を強められる可能性が示唆された。現在、熱傷創で黄色ブドウ球菌と並んで問題となっている緑膿菌に対しても抗菌活性や抗生剤の増強効果を検証中である。

• Usefulness of disease-specific microRNA for respiratory syncytial virus induced lower respiratory tract inflammation

  Grant-in-Aid for Young Scientists (B)

  Project Year :

  2016.04

  -

  2018.03

   

  Yamamoto Keisuke, HIMI Tetsuo, YOKOTA Shin-ichi, Takano Kenichi, KUROSE Makoto, KAMEKURA Ryuta, OHKUNI Tsuyoshi, OGASAWARA Noriko, YAMAMOTO Soh

  　View Summary

  (1)Clarithromycin (CAM) as a treatment of RSV infection and (2)disease-specific microRNA as an index of disease evaluation were examined.CAM treatment led to a significant reduction in RSV-mediated IL-8, CCL5, IFN-βand -λ production.Furthermore,IFN-β promoter activity (activated by poly I:C and RSV infection) was significantly reduced after treatment with CAM.CAM also inhibited IRF-3 dimerization and subsequent translocation to the nucleus.
  RSV infection-specific secreted miRNAs were identified. Housekeeping gene of nasal secreted miRNA was identified.

• Clarification of drug resistance of mucoid type Streptococcus pneumoniae

  Grant-in-Aid for Scientific Research (C)

  Project Year :

  2015.04

  -

  2018.03

   

  Miyamoto Atsushi

  　View Summary

  We obtained 51 mucoid strains from 1,061 Streptococcus pneumoniae clinical isolates collected in Hokkaido Prefecture, Japan. We evaluated biofilm formation, minimum biofilm eradication concentration of various antimicrobials, and growth rate. Significant differences between mucoid and non-mucoid strains were not observed. On the other hand, we found that Natto peptide, which is from a Japanese soy bean fermented food, showed specific bactericidal activity against S. pneumoniae, and Bacillus subtilis group of Bacillus genus. We clarified that its mechanism was failure of cell separation during cell division in S. pneumoniae. The Natto peptide showed similar antimicrobial activity against mucoid, non-mucoid, antimicrobial susceptible, and multidrug resistant strains of S. pneumoniae.

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