Periplasmic protein EipA determines envelope stress resistance and virulence in Brucella abortus.

BRUCELLA abortus; MICROBIAL virulence; INFECTION; TRANSPOSONS; MAMMALIAN cell cycle

Summary: Molecular components of the Brucella abortus cell envelope play a major role in its ability to infect, colonize and survive inside mammalian host cells. In this study, we have defined a role for a conserved gene of unknown function in B. abortus envelope stress resistance and infection. Expression of this gene, which we name eipA, is directly activated by the essential cell cycle regulator, CtrA. eipA encodes a soluble periplasmic protein that adopts an unusual eight‐stranded β‐barrel fold. Deletion of eipA attenuates replication and survival in macrophage and mouse infection models, and results in sensitivity to treatments that compromise the cell envelope integrity. Transposon disruption of genes required for LPS O‐polysaccharide biosynthesis is synthetically lethal with eipA deletion. This genetic connection between O‐polysaccharide and eipA is corroborated by our discovery that eipA is essential in Brucella ovis, a naturally rough species that harbors mutations in several genes required for O‐polysaccharide production. Conditional depletion of eipA expression in B. ovis results in a cell chaining phenotype, providing evidence that eipA directly or indirectly influences cell division in Brucella. We conclude that EipA is a molecular determinant of Brucella virulence that functions to maintain cell envelope integrity and influences cell division. We have characterized a conserved protein of unknown function, which we have named EipA. EipA plays a role in maintenance Brucella cell envelope integrity and is genetically linked to O‐polysaccharide synthesis. EipA influences features of the envelope that are important for Brucella spp. replication and survival in the host intracellular niche. [ABSTRACT FROM AUTHOR]

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