CsrA (BB0184) is not involved in activation of the RpoN-RpoS regulatory pathway in Borrelia burgdorferi.
Borrelia burgdorferi encodes a homologue of the bacterial carbon storage regulator A (CsrA). Recently, it was reported that CsrA contributes to B. burgdorferi infectivity and is required for the activation of the central RpoN-RpoS regulatory pathway. However, many questions concerning the function of CsrA in B. burgdorferi gene regulation remain unanswered. In particular, there are conflicting reports concerning the molecular details of how CsrA may modulate rpoS expression and, thus, how CsrA may influence the RpoN-RpoS pathway in B. burgdorferi. To address these key discrepancies, we examined the role of CsrA in differential gene expression in the Lyme disease spirochete. Upon engineering an inducible csrA expression system in B. burgdorferi, controlled hyperexpression of CsrA in a merodiploid strain did not significantly alter the protein and transcript levels of bosR, rpoS, and RpoS-dependent genes (such as ospC and dbpA). In addition, we constructed isogenic csrA mutants in two widely used infectious B. burgdorferi strains. When expression of bosR, rpoS, ospC, and dbpA was compared between the csrA mutants and their wild-type counterparts, no detectable differences were observed. Finally, animal studies indicated that the csrA mutants remained infectious for and virulent in mice. Analyses of B. burgdorferi gene expression in mouse tissues showed comparable levels of rpoS transcripts by the csrA mutants and the parental strains. Taken together, these results constitute compelling evidence that CsrA is not involved in activation of the RpoN-RpoS pathway and is dispensable for mammalian infectious processes carried out by B. burgdorferi.
Department of Microbiology, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
Zhiming
Z
Ouyang
Jianli
J
Zhou
Michael V
MV
Norgard
D000818:Animals; D001426:Bacterial Proteins / Q000502:physiology*; D025065:Borrelia burgdorferi / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D004268:DNA-Binding Proteins; D004195:Disease Models, Animal; D020869:Gene Expression Profiling; D015964:Gene Expression Regulation, Bacterial; D015151:Immunoblotting; D008193:Lyme Disease / Q000382:microbiology*; D051379:Mice; D051877:RNA Polymerase Sigma 54; D060888:Real-Time Polymerase Chain Reaction; D012097:Repressor Proteins / Q000502:physiology*; D012808:Sigma Factor / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D014774:Virulence
D001426:Bacterial Proteins; D004268:DNA-Binding Proteins; D012097:Repressor Proteins; D012808:Sigma Factor; C069567:sigma factor KatF protein, Bacteria; D051877:RNA Polymerase Sigma 54