The function and identification of the specific proteins of multidrug-resistant Escherichia coli ST131

• Project/Area Number: 18K16189
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 54030:Infectious disease medicine-related
• Research Institution: Tenri Health Care University
• Principal Investigator: Nakamura Akihiro 天理医療大学, 医療学部, 講師 (30647087)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2020: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2019: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2018: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: Escherichia coli / sequence type 131 / YahO / 可溶性チトクロームb562 / HdeA / YjbJ / ESBL / carbapenemase / proteomics / Escherichia coli ST131 / specific proteins / YnfD / cytochrome b562

Outline of Final Research Achievements

Escherichia coli ST131-specific proteins were detected, including YahO protein with E34A amino acid substitution with 7655 m/z (unknown function), soluble cytochrome b562 with 11783 m/z (unknown function), HdeA with 9710 m/z (acid stress response related), and YjbJ protein with 8351 m/z (unknown function). In addition, we found a sequence unique to ST131 C clade in soluble cytochrome b562 with 11783 m/z. The predicted protein-protein interactions of YahO and soluble cytochrome b562, whose functions are currently unknown, suggest that they may be related in biofilm formation.

Academic Significance and Societal Importance of the Research Achievements

ESBLやカルバペネマーゼを産生するEscherichia coli ST131の世界的なパンデミックが問題視されているが、その原因は未だ明らかになっていない。われわれはST131パンデミックの原因を追究すべく、MALDI-TOF MSを用いてST131特異的タンパク質を探索した。その結果主に4つのアミノ酸置換をともなうタンパク質を発見した。しかし、これらの中にはその機能が現在のところ不明なものが多く存在する。今後、これらの機能を明らかにすることにより、薬剤耐性菌が世界的パンデミックを引き起こす原因が追究できる可能性を秘めている。

Research Products

• [Journal Article] Novel strategy of rapid typing of Shiga toxin-producing Escherichia coli using MALDI Biotyper and ClinProTools analysis (2021)
  • Author(s): Kubo Yumi、Ueda Osamu、Nagamitsu Sawa、Yamanishi Hachiro、Nakamura Akihiro、Komatsu Masaru
  • Journal Title: Journal of Infection and Chemotherapy Volume: 18 Issue: 8 Pages: 00071-4
  • DOI: 10.1016/j.jiac.2021.03.002
  • Peer Reviewed
• [Journal Article] Evaluation of the detection ability of uropathogen morphology and vaginal contamination by the Atellica UAS800 automated urine microscopy analyzer and its effectiveness (2021)
  • Author(s): Nakamura Akihiro、Shinke Tetsuya、Noguchi Nobuyoshi、Komatsu Masaru、Yamanishi Hachiro
  • Journal Title: Journal of Clinical Laboratory Analysis Volume: 35 Issue: 3
  • DOI: 10.1002/jcla.23698
  • Peer Reviewed / Open Access
• [Journal Article] Fecal carriage and molecular epidemiologic characteristics of carbapenemase-producing Enterobacterales in primary care hospital in a Japanese city (2020)
  • Author(s): Ohno Yuki、Nakamura Akihiro、Hashimoto Eriko、Noguchi Nobuyoshi、Matsumoto Gaku、Fukuda Saori、Abe Noriyuki、Matsuo Shuji、Komatsu Masaru
  • Journal Title: Journal of Infection and Chemotherapy Volume: 26 Issue: 9 Pages: 928-932
  • DOI: 10.1016/j.jiac.2020.04.012
  • Peer Reviewed
• [Journal Article] Prediction of Uropathogens by Flow Cytometry and Dip-stick Test Results of Urine Through Multivariable Logistic Regression Analysis (2020)
  • Author(s): Nakamura Akihiro、Kohno Aya、Noguchi Nobuyoshi、Kawa Kenji、Ohno Yuki、Komatsu Masaru、Yamanishi Hachiro
  • Journal Title: PLOS ONE Volume: 15 Issue: 1 Pages: e0227257-e0227257
  • DOI: 10.1371/journal.pone.0227257
  • Peer Reviewed / Open Access
• [Journal Article] Prediction of Uropathogens by Flow Cytometry and Dip-stick Test Results of Urine Through Multivariable Logistic Regression Analysis (2020)
  • Author(s): Nakamura A, Kohno A, Noguchi N, Kawa K, Ohno Y, Komatsu M, Yamanishi H
  • Journal Title: PLoS One Volume: 15
  • Peer Reviewed / Open Access
• [Journal Article] 技術講座 一般 尿沈渣中の白血球形態とその鑑別 (2020)
  • Author(s): 中村彰宏
  • Journal Title: 検査と技術 Volume: 48 Pages: 118-123
• [Journal Article] Identification of specific protein amino acid substitutions of extended-spectrum β-lactamase (ESBL)-producing Escherichia coli ST131: a proteomics approach using mass spectrometry. (2019)
  • Author(s): Nakamura A, Komatsu M, Ohno Y, Noguchi N, Kondo A, Hatano N
  • Journal Title: Sci Rep Volume: 9 Pages: 8555-8555
  • Peer Reviewed / Open Access
• [Journal Article] Emergence of IMP-producing hypervirulent Klebsiella pneumoniae carrying a pLVPK-like virulence plasmid. (2019)
  • Author(s): Harada S, Aoki K, Ishii Y, Ohno Y, Nakamura A, Komatsu M, Tateda K
  • Journal Title: Int J Antimicrob Agents Volume: 53 Pages: 873-875
  • Peer Reviewed
• [Journal Article] A case of otitis externa caused by Schizophyllum commune: An approach to antimicrobial stewardship using Gram staining of otorrhea in a medical clinic. (2019)
  • Author(s): Maeda M, Maeda T, Nakamura A, Komatsu M
  • Journal Title: J Infect Chemother Volume: 25 Pages: 731-734
  • Peer Reviewed
• [Journal Article] 多剤耐性Escherichia coli sequence type 131が保有するYahO特異的アミノ酸変異E34Aが与えるタンパク質間相互作用および発現に関する研究 (2019)
  • Author(s): 中村彰宏、大野裕貴、野口延由、小松方
  • Journal Title: 天理医療大学紀要 Volume: 7 Pages: 16-21
  • NAID: 130007720953
  • Peer Reviewed
• [Journal Article] Next Generation Sequencerを用いた細菌の全ゲノム解析方法 (2019)
  • Author(s): 野口延由、中村彰宏、小松方
  • Journal Title: 天理医療大学紀要 Volume: 7 Pages: 37-40
  • NAID: 130007720969
  • Peer Reviewed
• [Journal Article] A case of otitis externa caused by Schizophyllum commune: an approach to antimicrobial stewardship using Gram staining of otorrhea in a medical clinic (2019)
  • Author(s): Maeda M, Maeda T, Nakamura A, Komatsu M
  • Journal Title: J Infect Chemother Volume: 21 Issue: 9 Pages: 30431-8
  • DOI: 10.1016/j.jiac.2019.03.005
  • Peer Reviewed
• [Journal Article] Evaluation of the modified carbapenem inactivation method for the detection of carbapenemase-producing Enterobacteriaceae. (2018)
  • Author(s): Kuchibiro T, Komatsu M, Yamasaki K, Nakamura T, Nishio H, Nishi I, Kimura K, Niki M, Ono T, Sueyoshi N, Kita M, Kida K, Ohama M, Satoh K, Toda H, Mizutani T, Fukuda N, Sawa K, Nakai I, Kofuku T, Orita T, Watari H, Shimura S, Fukuda S, Nakamura A, Wada Y.
  • Journal Title: J Infect Chemother Volume: 24 Issue: 4 Pages: 262-266
  • DOI: 10.1016/j.jiac.2017.11.010
  • Peer Reviewed
• [Presentation] BDマックスを用いた各種カルバペネマーゼ産生遺伝子Multiplex PCR融解曲線解析法の構築 (2021)
  • Author(s): 中村彰宏、太田嘉一、小松 方
  • Organizer: 第32回日本臨床微生物学会
• [Presentation] 多剤耐性腸内細菌目細菌における新規コリスチン耐性遺伝子mcr-9コーディングゲノム構造解析 (2021)
  • Author(s): 中村彰宏、中村竜也、仁木 誠、口広智一、西 功、小松 方
  • Organizer: 第32回日本臨床微生物学会
• [Presentation] 腸管感染症に有用な検査法とその役割 -分離培養および用手法同定法- (2021)
  • Author(s): 中村彰宏
  • Organizer: 第32回日本臨床微生物学会
  • Invited
• [Presentation] Comparison of beta-lactamase-producing Escherichia coli ST131 C1-M27 and ST131 non-C1-M27 by whole genome analysis using next-generation sequencing in Japan (2020)
  • Author(s): Nobuyoshi Noguchi, Akihiro Nakamura, Masaru Komatsu
  • Organizer: 30th European Congress of Clinical Microbiology and Infectious Diseases
  • Int'l Joint Research
• [Presentation] TOF-MSを極める～MALDI-TOFMSを用いたESBL産生Escherichia coli ST131パンデミッククローンのバイオマーカー探索とそのプロテオミクス解析 (2020)
  • Author(s): 中村彰宏
  • Organizer: 第30回日本臨床微生物学会
  • Invited
• [Presentation] 薬剤耐性菌の検査法～日常検査でここまでできる～：遺伝子検査は日常検査でこう活かせ！～ (2020)
  • Author(s): 中村彰宏
  • Organizer: 第30回日本臨床微生物学会
  • Invited
• [Presentation] Escherichia coli ST131のClade分類とGABA permeaseの遺伝子変異の関係性 (2020)
  • Author(s): 野口延由、中村彰宏、小松方
  • Organizer: 第30回日本臨床微生物学会
• [Presentation] 全ゲノム解析によるEscherichia coli ST131パンデミック要因の探索～C1-M27パンデミッククレードの特異的遺伝子変異の探索とその相互作用予測～ (2019)
  • Author(s): 野口延由、中村彰宏、小松方
  • Organizer: 第36回奈良県医学検査学会
• [Presentation] 求められる尿沈渣検査にするために～微生物・寄生虫～ (2019)
  • Author(s): 中村彰宏
  • Organizer: 第59回日臨技近畿支部医学検査学会
  • Invited
• [Presentation] 多剤耐性腸内細菌科細菌におけるコリスチン耐性状況とそのメカニズムに関する研究 (2019)
  • Author(s): 福田菜々子、中村彰宏、野口延由、大野裕貴、仁木誠、中村竜也、西功、小松方
  • Organizer: 第59回日臨技近畿支部医学検査学会
• [Presentation] 泌尿器疾患における尿一般検査の現状 (2019)
  • Author(s): 中村彰宏
  • Organizer: 第34回奈良県臨床細胞学会学術集会
  • Invited
• [Presentation] Desulfovibrio fairfieldensisによる菌血症の一例と文献レビュー (2019)
  • Author(s): 大野裕貴、阿部教行、松本学、橋本恵理子、福田砂織、河野久、中村彰宏、松尾収二
  • Organizer: 第68回日本医学検査学会
• [Presentation] Proteomics approach to identify the specific proteins of multple drug-resistant E. coli ST131 by MALDI-TOF MS (2018)
  • Author(s): Nakamura A
  • Organizer: 21th General Meeting The Korean Society of Clinical Microbiology
  • Int'l Joint Research / Invited
• [Presentation] ESBL産生大腸菌の進化とパンデミック～ゲノミクス、プロテオミクスレベルからみた考察～ (2018)
  • Author(s): 中村彰宏
  • Organizer: 第22回近畿耐性菌研究会特別講演会
• [Presentation] ESBL産生Escherichia coli ST131における特異的タンパク質同定とそのタンパク質間相互作用予測～ST131クレード別解析を含む～ (2018)
  • Author(s): 中村彰宏、野口延由、小松方
  • Organizer: 第30回日本臨床微生物学会総会・学術集会
• [Presentation] 尿一般検査領域における更なる付加価値情報を再考する～細菌類～ (2018)
  • Author(s): 中村彰宏
  • Organizer: 第58回日本臨床検査技師会近畿支部医学検査学会
  • Invited