DksA plays an essential role in regulating the virulence of Borrelia burgdorferi.
Animals
Antigens, Bacterial
/ metabolism
Bacterial Outer Membrane Proteins
/ metabolism
Bacterial Proteins
/ genetics
Borrelia burgdorferi
/ genetics
Gene Expression Regulation, Bacterial
/ genetics
Lyme Disease
/ microbiology
Mice
Mice, Inbred C3H
Sigma Factor
/ genetics
Starvation
/ genetics
Virulence
/ genetics
Virulence Factors
/ genetics
Borrelia burgdorferi
Lyme disease
gene regulation
pathogenesis
virulence
Journal
Molecular microbiology
ISSN: 1365-2958
Titre abrégé: Mol Microbiol
Pays: England
ID NLM: 8712028
Informations de publication
Date de publication:
07 2020
07 2020
Historique:
received:
04
03
2020
revised:
13
03
2020
accepted:
20
03
2020
pubmed:
1
4
2020
medline:
28
4
2021
entrez:
1
4
2020
Statut:
ppublish
Résumé
The RNA polymerase-binding protein DksA, together with the alarmone nucleotides (p)ppGpp, mediates the stringent response to nutrient starvation in Borrelia burgdorferi. To date, the contribution of DksA to B. burgdorferi infection remains unknown. We report here that DksA is essential for B. burgdorferi to infect a mammalian host. dksA expression was highly induced during infection. Moreover, a dksA-deficient mutant was incapable of infecting mice. The mutant displayed growth defects when cultured in vitro and resistance to osmotic pressure was markedly reduced. These phenotypes were fully restored to those of the wild type when dksA mutation was complemented. We further showed that DksA controlled the expression of virulence-associated lipoprotein OspC, likely via the central alternative sigma factor RpoS. Synthesis of RpoS was abolished in the dksA mutant, but rpoS transcription remained unaffected. Additionally, we found that the expression of clpX, clpA, clpP, and clpP2 was significantly increased in the mutant, suggesting that DksA may post-transcriptionally regulate rpoS expression via its effect on ClpXP and/or ClpAP proteases. These combined data demonstrate that DksA regulates B. burgdorferi virulence at least partially through its influence on RpoS and OspC. This study thus elucidates that, in addition to function as a stringent response regulator, DksA promotes the transcription and/or translation of genes contributing to B. burgdorferi infectivity.
Identifiants
pubmed: 32227372
doi: 10.1111/mmi.14504
pmc: PMC8331073
mid: NIHMS1584994
doi:
Substances chimiques
Antigens, Bacterial
0
Bacterial Outer Membrane Proteins
0
Bacterial Proteins
0
OspC protein
0
Sigma Factor
0
Virulence Factors
0
sigma factor KatF protein, Bacteria
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
172-183Subventions
Organisme : NIAID NIH HHS
ID : R03 AI146909
Pays : United States
Organisme : NIAID NIH HHS
ID : R21 AI119437
Pays : United States
Informations de copyright
© 2020 John Wiley & Sons Ltd.
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