Non-pathogenic Escherichia coli acquires virulence by mutating a growth-essential LPS transporter

English version

Autoři: Chikara Kaito ^aff001; Hirono Yoshikai ^aff002; Ai Wakamatsu ^aff003; Atsushi Miyashita ^aff002; Yasuhiko Matsumoto ^aff004; Tomoko Fujiyuki ^aff005; Masaru Kato ^aff006; Yoshitoshi Ogura ^aff007; Tetsuya Hayashi ^aff007; Takao Isogai ^aff008; Kazuhisa Sekimizu ^aff009
Působiště autorů: Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University, Kita-ku, Okayama, Japan ^aff001; Graduate School of Pharmaceutical Sciences, The University of Tokyo, Bunkyo-ku, Tokyo, Japan ^aff002; Japan Biological Informatics Consortium (JBIC), Koto-ku, Tokyo, Japan ^aff003; Department of Microbiology, Meiji Pharmaceutical University, Kiyose, Tokyo, Japan ^aff004; The Institute of Medical Science, The University of Tokyo, Minato-ku, Tokyo, Japan ^aff005; Devision of Bioanalytical Chemistry, School of Pharmacy, Showa University, Shinagawa-ku, Tokyo, Japan ^aff006; Department of Bacteriology, Faculty of Medical Sciences, Kyushu University, Fukuoka, Japan ^aff007; Translational Research Center, Fukushima Medical University, Fukushima, Japan ^aff008; Institute of Medical Mycology, Teikyo University, Hachioji, Tokyo, Japan ^aff009
Vyšlo v časopise: Non-pathogenic Escherichia coli acquires virulence by mutating a growth-essential LPS transporter. PLoS Pathog 16(4): e32767. doi:10.1371/journal.ppat.1008469
Kategorie: Research Article
doi: https://doi.org/10.1371/journal.ppat.1008469

Souhrn

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.

Klíčová slova:

Amino acid substitution – Antimicrobial resistance – Bacterial evolution – Mutagenesis – Mutant strains – Silkworms – Substitution mutation – Vancomycin

Zdroje

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