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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.

The Pathogenic Properties of a Novel and Conserved Gene Product, KerV, in Proteobacteria