RT Journal Article SR Electronic T1 Periplasmic protein EipA determines envelope stress resistance and virulence in Brucella abortus JF bioRxiv FD Cold Spring Harbor Laboratory SP 442541 DO 10.1101/442541 A1 Julien Herrou A1 Jonathan W. Willett A1 Aretha Fiebig A1 Lydia M. Varesio A1 Daniel M. Czyż A1 Jason X. Cheng A1 Eveline Ultee A1 Ariane Briegel A1 Lance Bigelow A1 Gyorgy Babnigg A1 Youngchang Kim A1 Sean Crosson YR 2018 UL http://biorxiv.org/content/early/2018/11/20/442541.abstract AB 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 integrity of the cell envelope. 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.