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ID 59919
フルテキストURL
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著者
Kaito, Chikara Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University ORCID Kaken ID publons
Yoshikai, Hirono Graduate School of Pharmaceutical Sciences, The University of Tokyo
Wakamatsu, Ai Japan Biological Informatics Consortium (JBIC)
Miyashita, Atsushi Graduate School of Pharmaceutical Sciences, The University of Tokyo
Matsumoto, Yasuhiko Department of Microbiology, Meiji Pharmaceutical University
Fujiyuki, Tomoko The Institute of Medical Science, The University of Tokyo
Kato, Masaru Devision of Bioanalytical Chemistry, School of Pharmacy,Showa University
Ogura, Yoshitoshi Department of Bacteriology, Faculty of Medical Sciences,Kyushu University
Hayashi, Tetsuya Department of Bacteriology, Faculty of Medical Sciences,Kyushu University
Isogai, Takao Translational Research Center, Fukushima Medical University
Sekimizu, Kazuhisa Institute of Medical Mycology, Teikyo University
抄録
The molecular mechanisms that allow pathogenic bacteria to infect animals have been intensively studied. On the other hand, the molecular mechanisms by which bacteria acquire virulence functions are not fully understood. In the present study, we experimentally evaluated the evolution of a non-pathogenic strain of Escherichia coli in a silkworm infection model and obtained pathogenic mutant strains. As one cause of the high virulence properties of E. coli mutants, we identified amino acid substitutions in LptD (G580S) and LptE (T95I) constituting the lipopolysaccharide (LPS) transporter, which translocates LPS from the inner to the outer membrane and is essential for E. coli growth. The growth of the LptD and LptE mutants obtained in this study was indistinguishable from that of the parent strain. The LptD and LptE mutants exhibited increased secretion of outer membrane vesicles containing LPS and resistance against various antibiotics, antimicrobial peptides, and host complement. In vivo cross-linking studies revealed that the conformation of the LptD-LptE complex was altered in the LptD and LptE mutants. Furthermore, several clinical isolates of E. coli carried amino acid substitutions of LptD and LptE that conferred resistance against antimicrobial substances. This study demonstrated an experimental evolution of bacterial virulence properties in an animal infection model and identified functional alterations of the growth-essential LPS transporter that led to high bacterial virulence by conferring resistance against antimicrobial substances. These findings suggest that non-pathogenic bacteria can gain virulence traits by changing the functions of essential genes, and provide new insight to bacterial evolution in a host environment. Author summary Pathogenic bacteria developed their virulence properties by changing the functions of various genes after the emergence of the host animals on earth. The types of gene function alterations that confer bacterial virulence properties, however, have remained unclear. We utilized a silkworm infection model to perform an experimental evolution of bacterial virulence activity. From a non-pathogenic strain of Escherichia coli, we obtained a mutant strain that exhibited 500-fold higher virulence than the original strain and identified mutations of the lipopolysaccharide (LPS) transporter, which translocates LPS onto the bacterial surface, as one cause of the high virulence. The mutations changed the structure of the LPS transporter, increased the secretion of outer membrane vesicles, and enabled bacterial survival in the presence of host antimicrobial substances. This mechanism to gain high virulence occurs naturally, as several E. coli clinical isolates carried mutations of the LPS transporter that confer resistance against antimicrobial substances. Our study unveiled a novel mechanism by which bacteria increase their virulence through modifying their gene function.
発行日
2020-04-23
出版物タイトル
PLoS Pathogens
16巻
4号
出版者
Public Library of Science
開始ページ
e1008469
ISSN
1553-7366
資料タイプ
学術雑誌論文
言語
English
OAI-PMH Set
岡山大学
著作権者
© 2020 Kaito et al.
論文のバージョン
publisher
PubMed ID
DOI
Web of Science KeyUT
関連URL
isVersionOf https://doi.org/10.1371/journal.ppat.1008469
ライセンス
https://creativecommons.org/licenses/by/4.0/
Citation
Kaito C, Yoshikai H, Wakamatsu A, et al. Non-pathogenic Escherichia coli acquires virulence by mutating a growth-essential LPS transporter. PLoS Pathog. 2020;16(4):e1008469. Published 2020 Apr 23. doi:10.1371/journal.ppat.1008469
助成機関名
日本学術振興会
助成番号
16H06279
15H04727
15H05783
19H03466
19K22523