Characterization of a Conditional bosR Mutant in Borrelia burgdorferi

• Published in: Infection and Immunity Vol. 78; no. 1; pp. 265 - 274
• Main Authors: Hyde, Jenny A, Shaw, Dana K, Smith, Roger III, Trzeciakowski, Jerome P, Skare, Jon T
• Format: Journal Article
• Language: English
• Published: Washington, DC American Society for Microbiology 01.01.2010; American Society for Microbiology (ASM)
• Subjects: Arthropoda; Bacterial Proteins - genetics; Bacterial Proteins - metabolism; Bacteriology; Biological and medical sciences; Borrelia burgdorferi; Borrelia burgdorferi - drug effects; Borrelia burgdorferi - genetics; Borrelia burgdorferi - metabolism; Carbon dioxide; Fundamental and applied biological sciences. Psychology; Gene expression; Gene Expression Regulation, Bacterial - physiology; Homeostasis; Hydrogen peroxide; Hydrogen Peroxide - pharmacology; Life cycle; Lyme disease; Lymphocytes B; Microbiology; Miscellaneous; Molecular Pathogenesis; Mutation; Oxidative Stress; SodA protein; Temperature effects; Virulence; Bacteria; Borrelia burgdorferi; Mutation; Spirochaetaceae; Spirochaetales; Immunity
• ISSN: 0019-9567; 1098-5522
• DOI: 10.1128/IAI.01018-09

Borrelia burgdorferi, the etiological agent of Lyme disease, adapts to unique host environments as a consequence of its complex life cycle that spans both arthropod and mammalian species. In this regard, B. burgdorferi must adapt to various environmental signals, pHs, temperatures, and O₂ and CO₂ levels to establish infectious foci. We hypothesize that the BosR protein functions as a global regulator that is required for both borrelial oxidative homeostasis and pathogenesis. To assess the role of BosR in B. burgdorferi, we constructed an IPTG (isopropyl-β-D-thiogalactopyranoside)-regulated bosR strain. The selective decrease of bosR resulted in a change in growth when cells were cultured either anaerobically or microaerobically; however, a distinct growth defect was observed for anaerobically grown B. burgdorferi relative to the growth attenuation observed for microaerobically grown B. burgdorferi. B. burgdorferi cells in which BosR levels were reduced were more sensitive to hydrogen peroxide and produced lower levels of NapA (Dps) and SodA, proteins involved in the oxidative stress response. In addition, the levels of OspC and DbpA were also induced coincident with increased BosR levels, suggesting that BosR interfaces with the RpoS regulatory cascade, which is known to modulate virulence gene expression in B. burgdorferi. Taken together, these results indicate that BosR is involved in the resistance of B. burgdorferi to oxidative stressors and affects the expression of genes, either directly or indirectly, whose products are important in borrelial pathogenesis.