RRC ID 65962
Author Kaito C, Yoshikai H, Wakamatsu A, Miyashita A, Matsumoto Y, Fujiyuki T, Kato M, Ogura Y, Hayashi T, Isogai T, Sekimizu K.
Title Non-pathogenic Escherichia coli acquires virulence by mutating a growth-essential LPS transporter.
Journal PLoS Pathog
Abstract 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.
Volume 16(4)
Pages e1008469
Published 2020-4-1
DOI 10.1371/journal.ppat.1008469
PII PPATHOGENS-D-19-01261
PMID 32324807
PMC PMC7179839
MeSH Animals Bacterial Outer Membrane Proteins / genetics* Bacterial Outer Membrane Proteins / metabolism Biological Transport Bombyx / microbiology Cell Membrane / metabolism Escherichia coli / genetics* Escherichia coli / metabolism Escherichia coli / pathogenicity* Escherichia coli Proteins / genetics* Escherichia coli Proteins / metabolism Lipopolysaccharides / metabolism Models, Molecular Protein Binding Virulence / physiology
IF 6.463
Resource
Silkworms