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

被引:16
作者
Herrou, Julien [1 ]
Willett, Jonathan W. [1 ]
Fiebig, Aretha [1 ]
Varesio, Lydia M. [1 ]
Czyz, Daniel M. [2 ]
Cheng, Jason X. [3 ]
Ultee, Eveline [4 ]
Briegel, Ariane [4 ]
Bigelow, Lance [5 ]
Babnigg, Gyorgy [5 ]
Kim, Youngchang [5 ]
Crosson, Sean [1 ]
机构
[1] Univ Chicago, Dept Biochem & Mol Biol, 920 E 58th St, Chicago, IL 60637 USA
[2] Univ Florida, Dept Microbiol & Cell Sci, Gainesville, FL 32611 USA
[3] Univ Chicago, Dept Pathol, 5841 S Maryland Ave, Chicago, IL 60637 USA
[4] Leiden Univ, Dept Biol, Leiden, Netherlands
[5] Argonne Natl Lab, Biosci Div, 9700 S Cass Ave, Argonne, IL 60439 USA
基金
美国国家卫生研究院;
关键词
CELL-CYCLE TRANSCRIPTION; ESCHERICHIA-COLI; UNDECAPRENYL-PHOSPHATE; TYROSINE PHOSPHATASES; RESPONSE REGULATOR; O-POLYSACCHARIDE; GENE-EXPRESSION; GLOBAL ANALYSIS; LIPOPOLYSACCHARIDE; BIOSYNTHESIS;
D O I
10.1111/mmi.14178
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 beta-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.
引用
收藏
页码:637 / 661
页数:25
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