4.4 Article

Inactivation of bb0184, Which Encodes Carbon Storage Regulator A, Represses the Infectivity of Borrelia burgdorferi

Journal

INFECTION AND IMMUNITY
Volume 79, Issue 3, Pages 1270-1279

Publisher

AMER SOC MICROBIOLOGY
DOI: 10.1128/IAI.00871-10

Keywords

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Funding

  1. Public Service [AI073354, AI078958]
  2. American Heart Association

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The genome of Borrelia burgdorferi, the Lyme disease spirochete, encodes a homolog (the bb0184 gene product) of the carbon storage regulator A protein (CsrA(Bb)); recent studies reported that CsrA(Bb) is involved in the regulation of several infectivity factors of B. burgdorferi. However, the mechanism involved remains unknown. In this report, a CsrA(Bb) mutant was constructed and complemented in an infectious B31A3 strain. Subsequent animal studies showed that the mutant failed to establish an infection in mice, highlighting that CsrA(Bb) is required for the infectivity of B. burgdorferi. Western blot analyses revealed that the virulence-associated factors OspC, DbpB, and DbpA were attenuated in the CsrA(Bb) mutant. The Rrp2-RpoN-RpoS pathway (sigma(54)-sigma(s) sigma factor cascade) is a central regulon that governs the expression of ospC, dbpB, and dbpA. Further analyses found that the level of RpoS was significantly decreased in the mutant, while the level of Rrp2 remained unchanged. A recent study reported that the overexpression of BB0589, a phosphate acetyl-transferase (Pta) that converts acetyl-phosphate to acetyl-coenzyme A (CoA), led to the inhibition of RpoS and OspC expression, suggesting that acetyl-phosphate is an activator of Rrp2. Along with this report, we found that CsrA(Bb) binds to the leader sequence of the bb0589 transcript and that the intracellular level of acetyl-CoA in the CsrA(Bb) mutant was significantly increased compared to that of the wild type, suggesting that more acetyl-phosphate was being converted to acetyl-CoA in the mutant. Collectively, these results suggest that CsrA(Bb) may influence the infectivity of B. burgdorferi via regulation of acetate metabolism and subsequent activation of the Rrp2-RpoN-RpoS pathway.

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