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

• Published in: Molecular microbiology Vol. 74; no. 6; pp. 1344 - 1355
• Main Authors: Hyde, Jenny A, Shaw, Dana K, Smith III, Roger, Trzeciakowski, Jerome P, Skare, Jon T
• Format: Journal Article
• Language: English
• Published: Oxford, UK Oxford, UK : Blackwell Publishing Ltd 01.12.2009; Blackwell Publishing Ltd
• Subjects: Animal Structures - microbiology; Animals; Arthropoda; Bacteria; Bacterial proteins; Bacterial Proteins - biosynthesis; Bacterial Proteins - genetics; Bacterial Proteins - physiology; Borrelia burgdorferi; Borrelia burgdorferi - drug effects; Borrelia burgdorferi - pathogenicity; Borrelia burgdorferi - physiology; Cells; DNA Transposable Elements; DNA-Binding Proteins - deficiency; DNA-Binding Proteins - genetics; DNA-Binding Proteins - physiology; Gene Deletion; Gene Expression Regulation, Bacterial; Humans; Hydrogen Peroxide - toxicity; Lyme disease; Lyme Disease - microbiology; Mice; Mice, Inbred C3H; Microbial Viability; Microbiology; Mutagenesis, Insertional; Oxidative Stress; Protein synthesis; Rodents; Sigma Factor - biosynthesis; Stress, Physiological; Virulence; Virulence Factors - biosynthesis
• ISSN: 0950-382X; 1365-2958
• DOI: 10.1111/j.1365-2958.2009.06951.x

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.