Feo is the most widespread and conserved system for ferrous iron uptake in bacteria, and it is important for virulence in several gastrointestinal pathogens. However, its mechanism remains poorly understood. Hitherto, most studies regarding the Feo system were focused on Gammaproteobacterial models, which possess three feo genes (feoA, B, and C) clustered in an operon. We found that the human pathogen Helicobacter pylori possesses a unique arrangement of the feo genes, in which only feoA and feoB are present and encoded in distant loci. In this study, we examined the functional significance of this arrangement.
Vibrio cholerae is a Gram-negative pathogen, living in constant competition with other bacteria in marine environments and during human infection. One competitive advantage of V. cholerae is the ability to metabolize diverse carbon sources, such as chitin and citrate. We observed that when some V. cholerae strains were grown on a medium with citrate, the medium’s chemical composition turned into a hostile alkaline environment for Gram-negative bacteria, such as Escherichia coli and Shigella flexneri. We found that although the ability to exclude competing bacteria was not contingent on exogenous citrate, V. cholerae C6706 citrate metabolism mutants ΔoadA-1, ΔcitE, and ΔcitF were not able to inhibit S. flexneri or E. coli growth. Lastly, we demonstrated that while the V. cholerae C6706-mediated increased medium pH was necessary for the enteric exclusion phenotype, secondary metabolites, such as bicarbonate (protonated to carbonate in the raised pH) from the metabolism of citrate, enhanced the ability to inhibit the growth of E. coli. These data provide a novel example of how V. cholerae outcompetes other Gram-negative bacteria.