title: 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.
abstract: Summary 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::kan(R) 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.
authors.affiliation: Department of Microbial and Molecular Pathogenesis, College of Medicine, Texas A&M Health Science Center, College Station, TX 77843-1114, USA.
authors.forename: Jenny A
authors.initials: JA
authors.lastname: Hyde
authors.forename: Dana K
authors.initials: DK
authors.lastname: Shaw
authors.forename: Roger
authors.initials: R
authors.lastname: Smith Iii
authors.forename: Jerome P
authors.initials: JP
authors.lastname: Trzeciakowski
authors.forename: Jon T
authors.initials: JT
authors.lastname: Skare
mesh_terms: D000825:Animal Structures / Q000382:microbiology; D000818:Animals; D001426:Bacterial Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D025065:Borrelia burgdorferi / Q000187:drug effects / Q000472:pathogenicity / Q000502:physiology*; D004251:DNA Transposable Elements; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D017353:Gene Deletion; D015964:Gene Expression Regulation, Bacterial; D006801:Humans; D006861:Hydrogen Peroxide / Q000633:toxicity; D008193:Lyme Disease / Q000382:microbiology; D051379:Mice; D008809:Mice, Inbred C3H; D050296:Microbial Viability; D016254:Mutagenesis, Insertional; D018384:Oxidative Stress; D012808:Sigma Factor / Q000096:biosynthesis*; D013312:Stress, Physiological; D014774:Virulence; D037521:Virulence Factors / Q000096:biosynthesis*
chemical_list: D001426:Bacterial Proteins; D004251:DNA Transposable Elements; D004268:DNA-Binding Proteins; D012808:Sigma Factor; D037521:Virulence Factors; C069567:sigma factor KatF protein, Bacteria; D006861:Hydrogen Peroxide