Abstract
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.
Highlights
Important infection mechanisms are often shared across diverse bacterial pathogens [1,2,3,4,5,6]
The ability of P.a.-kerV to proliferate within Arabidopsis leaves and cause disease symptoms was assessed in the P. aeruginosa Arabidopsis infiltration model, which involves forced insertion of suspended bacterial cells into the intercellular space of Arabidopsis leaves
We applied a combined approach of bench experiments and bioinformatics analyses to identify novel virulence determinants. We discovered such a factor KerV in P. aeruginosa, V. cholera, and Y. pseudotuberculosis
Summary
Important infection mechanisms are often shared across diverse bacterial pathogens [1,2,3,4,5,6]. Discovering broadly conserved virulence factors faces great challenges caused by the practical limitation mammalian hosts pose in high-throughput approaches [7]. This limitation has been considerably circumvented following the discovery that important virulence factors and corresponding pathways are conserved across a spectrum of hosts ranging from amoebae to mice [2,8,9,10,11]. This conservation made non-vertebrates amenable surrogate hosts for studying mammalian pathogenesis and added the benefit of enabling broadly conserved virulence factors to be identified. Yeasts [12], plants [13], nematodes [14], fruit flies [15], and zebrafish [16] have all been successfully applied in pathogenesis experiments
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