Education 【 display / non-display 】

Education 【 display / non-display 】

• 2007

  -

  2010

  Akita University   Graduate School of Engineering and Resource Science   Department of Advanced Materials Engineering  

• 2005

  -

  2007

  Akita University   Graduate School of Engineering and Resource Science   Department of Materials-process Engineering and Applied Chemistry for Environments  

• 2001

  -

  2005

  Akita University   Faculty of Engineering and Resource Science   環境物質工学科  

Research Experience 【 display / non-display 】

Research Experience 【 display / non-display 】

• 2016.04

  -

  2018.03

  Northwestern大学   Department of Cell and Molecular Biology   客員研究員

  客員研究員

• 2011.06

  -

  Now

  Sapporo Medical University   School of Medicine   助教

  助教

• 2010.04

  -

  2011.05

  Akita University   博士研究員

  博士研究員

Research Areas 【 display / non-display 】

Research Areas 【 display / non-display 】

• Life sciences   Immunology   自然免疫

• Life sciences   Virology   RNAウィルス

• Life sciences   Pharmaceuticals - health and biochemistry  

Affiliation 【 display / non-display 】

Affiliation 【 display / non-display 】

• Sapporo Medical University   医学部   助教  

Research Interests 【 display / non-display 】

Research Interests 【 display / non-display 】

• 分子シャペロン

• 自然免疫

• 炎症

• ミトコンドリア

• Toll-like receptor

display all >>

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

• 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]

  　View Summary

  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]

  　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

• 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]

  　View Summary

  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

display all >>

Misc 【 display / non-display 】

Misc 【 display / non-display 】

• 納豆由来ペプチドの特異な殺菌効果とその作用機序

  白石宗, 北川学, 山本聡, 久富亮佑, 佐藤豊孝, 涌井秀樹, 伊藤英晃, 宮本篤, 横田伸一

  エンドトキシン・自然免疫研究20－自然免疫における化学生物学の貢献－ ( 日本エンドトキシン・自然免疫研究会 )  20   39 - 42  2017

  Article, review, commentary, editorial, etc. (other)  

• 哺乳類HSP60の新規基質であるNIP-SNAP2タンパク質の機能

  山本聡, 小笠原徳子, 白石宗, 佐藤豊孝, 氷見徹夫, 伊藤英晃, 横田伸一

  臨床ストレス応答学会大会抄録集   10th  2015

  J-GLOBAL

• 排膿散及湯はインターフェロン産生誘導薬か?

  松田三千雄, 山本聡, 岡林環樹

  漢方医学   38 ( 2 ) 123 - 126  2014.06

  J-GLOBAL

Awards 【 display / non-display 】

Awards 【 display / non-display 】

• United Japanese Researchers Around the World paper award

  2020.03   United Japanese Reserchers Around the World   Differential roles of chronic autophagy in insulin production and sensitivity., Cell Reports, 2018, 23, 3286-3299.

• 海外留学助成金

  2016.03   上原記念生命科学財団  

  Winner： 山本聡

• 海外留学助成金

  2016.03   伊藤医薬学術交流財団  

  Winner： 山本聡

Research Projects 【 display / non-display 】

Research Projects 【 display / non-display 】

• 深在性真菌症のFFPE組織を用いた分子形態学的な同定および解析方法の確立

  基盤研究(C)

  Project Year :

  2022.04

  -

  2025.03

   

  青山 智志, 高澤 啓, 山本 聡

• Identification of host factors for Respiratory syncytial virus

  Grant-in-Aid for Scientific Research (C)

  Project Year :

  2022.04

  -

  2025.03

   

  山本 聡, 小笠原 徳子, 高澤 啓

• 次世代の耐性菌対策を考慮した、国際的ハイリスク病原性細菌の市中内定着様式の解明

  基盤研究(B)

  Project Year :

  2021.04

  -

  2024.03

   

  佐藤 豊孝, 浦野 恵美子, 青木 弘太郎, 中島 千絵, 臼井 優, 鈴木 仁人, 大久保 寅彦, 福田 昭, 小笠原 徳子, 山本 聡

  　View Summary

  本研究では、フルオロキノロン耐性大腸菌ST131をモデルに、『院内』で問題となるAMR感染症を『院外(市中)』からのプローチでその伝播・定着様式を明らかにすることで、現行のAMR対策が報われない国際的なAMR問題の根本的解決に繋がる次世代型(院内-市中一体型)AMR対策に資する科学的知見を提供することが本研究の目的である。本目的達成の為、本年度は、ST131の伝播状況と伝播様式および定着メカニズム(定着因子の同定)を行なった。具体的には、同一地域（札幌市内）から同一時期に院内及び市中の各サンプル群(患者、健常者、動物、環境)から大腸菌を一斉に分離した。その後、シプロフロキサシンに耐性だった株を対象にST131の検出PCRおよび次世代シーケンス解析により行なった。その結果、ヒトの臨床検体(大学病院)からは25%, ヒトの臨床検体(市中クリニック)からは19.2%, ヒトの健常者の便検体からは16.1%, 伴侶動物(犬や猫)の直腸スワブからは18.3%, 家畜の牛、豚、鶏の便検体からはそれぞれ9.5%, 0%, 6.7%のフルオロキノロン耐性率であった。分離大腸菌全体に占めるST131の割合は、ヒトの臨床検体(大学病院)からは12.5%, ヒトの臨床検体(市中クリニック)からは5.7%, ヒトの健常者の便検体からは8.2%, 伴侶動物(犬や猫)の直腸スワブからは15.9%, 家畜の牛、豚、鶏の便検体からは1株も分離されなかった。

• TLR10の多様性に注目した胃がん発がん機構の解析

  基盤研究(C)

  Project Year :

  2020.04

  -

  2024.03

   

  永島 裕之, 山本 聡, 加藤 淳二, 白石 宗

  　View Summary

  これまでTLR10はヒトに10あるTLRのうち、機能が判明していないTLRであると報告されていて、関連する感染症すら報告がない状態であった。しかし我々はHelicobater pylori感染がTLR10と強い関係を示すことを発見した。以下の問を設定し研究を行っている。 1)H.pyloriの特異的なLPSの構造がTLR10に認識されるのではないか、 2)TLR10のSNPによってH. pyloriの病原性に違いがあるのではないか 今回の研究に対して以下の実績を得ている 1)TLR10のリガンドの解析を行った。大阪大学深瀬教授の研究室から合成Lipid Aを入手し、HEK-cellにTLR10を遺伝子導入し、NF-kBの活性を測定。Helicobacter pylori LPSで刺激することで、NF-kBの活性を認めた。TLR10のリガンドの構造解析で良好な結果を得た。さらに同様の構造を有する合成リポタンパク質で同様の結果が得られるかを解析している最中である。これまで不明とされていたTLR10のリガンドの構造パターンを決定づける結果が得られている。 2) TLR10のSNPと胃粘膜のサイトカイン、病理組織変化に関する解析を行った。TLR10 SNPによって病理学的な炎症反応の違い、サイトカイン（IL-8等）の発現の違いがあるとの結果を得た。現在論文作成中となっている。

• 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, 佐藤 豊孝, 白石 宗, 永島 裕之

  　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

display all >>