The BosR regulatory protein of Borrelia burgdorferi interfaces with the RpoS regulatory pathway and modulates both the oxidative stress response and pathogenic properties of the Lyme disease spirochete
Open Access
- 10 December 2009
- journal article
- Published by Wiley in Molecular Microbiology
- Vol. 74 (6), 1344-1355
- https://doi.org/10.1111/j.1365-2958.2009.06951.x
Abstract
Borrelia burgdorferi, the Lyme disease spirochete, adapts as it moves between the arthropod and mammalian hosts that it infects. We hypothesize that BosR serves as a global regulator in B. burgdorferi to modulate the oxidative stress response and adapt to mammalian hosts. To test this hypothesis, a bosR mutant in a low‐passage B. burgdorferi isolate was constructed. The resulting bosR::kanR strain was altered when grown microaerobically or anaerobically suggesting that BosR is required for optimal replication under both growth conditions. The absence of BosR increased the sensitivity of B. burgdorferi to hydrogen peroxide and reduced the synthesis of Cdr and NapA, proteins important for cellular redox balance and the oxidative stress response, respectively, suggesting an important role for BosR in borrelial oxidative homeostasis. For the bosR mutant, the production of RpoS was abrogated and resulted in the loss of OspC and DbpA, suggesting that BosR interfaces with the Rrp2–RpoN–RpoS regulatory cascade. Consistent with the linkage to RpoS, cells lacking bosR were non‐infectious in the mouse model of infection. These results indicate that BosR is required for resistance to oxidative stressors and provides a regulatory response that is necessary for B. burgdorferi pathogenesis.This publication has 76 references indexed in Scilit:
- Characterization of a ConditionalbosRMutant inBorrelia burgdorferiInfection and Immunity, 2010
- Borrelia burgdorferi Lacking DbpBA Exhibits an Early Survival Defect during Experimental InfectionInfection and Immunity, 2008
- Essential Role of the Response Regulator Rrp2 in the Infectious Cycle of Borrelia burgdorferiInfection and Immunity, 2008
- Borrelia burgdorferi membranes are the primary targets of reactive oxygen speciesMolecular Microbiology, 2008
- Both Decorin-Binding Proteins A and B Are Critical for the Overall Virulence of Borrelia burgdorferiInfection and Immunity, 2008
- Analysis of the RpoS regulon in Borrelia burgdorferi in response to mammalian host signals provides insight into RpoS function during the enzootic cycleMolecular Microbiology, 2007
- Insights into the complex regulation of rpoS in Borrelia burgdorferiMolecular Microbiology, 2007
- Regulators of Expression of the Oligopeptide Permease A Proteins of Borrelia burgdorferiJournal of Bacteriology, 2007
- Rapid Clearance of Lyme Disease Spirochetes Lacking OspC from SkinInfection and Immunity, 2007
- Borrelia burgdorferi Alters Its Gene Expression and Antigenic Profile in Response to CO 2 LevelsJournal of Bacteriology, 2007