The pathogenic properties of a novel and conserved gene product, KerV, in proteobacteria.
Identification of novel virulence factors is essential for understanding bacterial pathogenesis and designing antibacterial strategies. In this study, we uncover such a factor, termed KerV, in Proteobacteria. Experiments carried out in a variety of eukaryotic host infection models revealed that the virulence of a Pseudomonas aeruginosa kerV null mutant was compromised when it interacted with amoebae, plants, flies, and mice. Bioinformatics analyses indicated that KerV is a hypothetical methyltransferase and is well-conserved across numerous Proteobacteria, including both well-known and emerging pathogens (e.g., virulent Burkholderia, Escherichia, Shigella, Vibrio, Salmonella, Yersinia and Brucella species). Furthermore, among the 197 kerV orthologs analyzed in this study, about 89% reside in a defined genomic neighborhood, which also possesses essential DNA replication and repair genes and detoxification gene. Finally, infection of Drosophila melanogaster with null mutants demonstrated that KerV orthologs are also crucial in Vibrio cholerae and Yersinia pseudotuberculosis pathogenesis. Our findings suggested that KerV has a novel and broad significance as a virulence factor in pathogenic Proteobacteria and it might serve as a new target for antibiotic drug design.
Department of Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, United States of America.
Dingding
D
An
Yiorgos
Y
Apidianakis
Ana Laura
AL
Boechat
Regina L
RL
Baldini
Boyan C
BC
Goumnerov
Laurence G
LG
Rahme
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D017360:Arabidopsis / Q000382:microbiology*; D001426:Bacterial Proteins / Q000378:metabolism*; D019295:Computational Biology / Q000379:methods; D017124:Conserved Sequence; D004331:Drosophila melanogaster / Q000378:metabolism; D015964:Gene Expression Regulation, Bacterial; D006801:Humans; D008780:Methyltransferases / Q000235:genetics / Q000502:physiology*; D051379:Mice; D010802:Phylogeny; D020560:Proteobacteria / Q000378:metabolism; D014734:Vibrio cholerae / Q000378:metabolism; D037521:Virulence Factors / Q000378:metabolism; D015011:Yersinia pseudotuberculosis / Q000378:metabolism
D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D037521:Virulence Factors; D008780:Methyltransferases