Periplasmic protein EipA determines envelope stress resistance and virulence in Brucella abortus.
Animals
Brucella abortus
/ enzymology
Brucella ovis
/ genetics
Brucellosis
/ microbiology
Cell Cycle
Cell Wall
/ metabolism
Disease Models, Animal
Gene Deletion
Gene Knockdown Techniques
Genes, Bacterial
Genes, Essential
Histocytochemistry
Macrophages
/ microbiology
Mice, Inbred BALB C
Microbial Viability
O Antigens
/ metabolism
Periplasmic Proteins
/ chemistry
Protein Conformation
Protein Folding
Spleen
/ pathology
Virulence Factors
/ chemistry
Journal
Molecular microbiology
ISSN: 1365-2958
Titre abrégé: Mol Microbiol
Pays: England
ID NLM: 8712028
Informations de publication
Date de publication:
03 2019
03 2019
Historique:
accepted:
30
11
2018
pubmed:
12
12
2018
medline:
3
8
2019
entrez:
12
12
2018
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 30536925
doi: 10.1111/mmi.14178
pmc: PMC6417958
mid: NIHMS1001021
doi:
Substances chimiques
O Antigens
0
Periplasmic Proteins
0
Virulence Factors
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Pagination
637-661Subventions
Organisme : NIAID NIH HHS
ID : R01 AI107159
Pays : United States
Organisme : NIAID NIH HHS
ID : U19 AI107792
Pays : United States
Organisme : NIH HHS
ID : R01AI107159
Pays : United States
Organisme : NIH HHS
ID : U19AI107792
Pays : United States
Commentaires et corrections
Type : CommentIn
Informations de copyright
© 2018 John Wiley & Sons Ltd.
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