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


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): e1008469. doi:10.1371/journal.ppat.1008469
Kategorie: Research Article
doi: 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


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