title: BosR (BB0647) governs virulence expression in Borrelia burgdorferi.
abstract: Summary Borrelia burgdorferi (Bb), the Lyme disease spirochaete, encodes a potential ferric uptake regulator (Fur) homologue, BosR (BB0647). Thus far, a role for BosR in Bb metabolism, gene regulation or pathogenesis has not been determined, largely due to the heretofore inability to inactivate bosR in low-passage, infectious Bb isolates. Herein, we report the generation of the first bosR-deficient mutant in a virulent strain of Bb. Whereas the bosR mutant persisted normally in ticks, the mutant was unable to infect mice, indicating that BosR is essential for Bb infection of a mammalian host. Moreover, transcriptional profiling of the bosR mutant showed that a number of genes were either positively or negatively influenced by BosR deficiency, suggesting that BosR may function both as a global repressor and activator in Bb. Strikingly, our study showed that BosR controls the expression of two major virulence-associated Bb lipoproteins, OspC and DbpA, likely via an influence on the alternative sigma factor, RpoS. This study thus not only has elucidated another key virulence gene of Bb, but also provides new insights into a previously unknown layer of gene regulation governing RpoS in Bb.
authors.affiliation: Department of Microbiology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
authors.forename: Zhiming
authors.initials: Z
authors.lastname: Ouyang
authors.forename: Manish
authors.initials: M
authors.lastname: Kumar
authors.forename: Toru
authors.initials: T
authors.lastname: Kariu
authors.forename: Shayma
authors.initials: S
authors.lastname: Haq
authors.forename: Martin
authors.initials: M
authors.lastname: Goldberg
authors.forename: Utpal
authors.initials: U
authors.lastname: Pal
authors.forename: Michael V
authors.initials: MV
authors.lastname: Norgard
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000502:physiology*; D025065:Borrelia burgdorferi / Q000235:genetics / Q000472:pathogenicity*; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D017353:Gene Deletion; D020869:Gene Expression Profiling; D015964:Gene Expression Regulation, Bacterial; D055786:Gene Knockout Techniques; D006801:Humans; D008193:Lyme Disease / Q000382:microbiology*; D051379:Mice; D013987:Ticks / Q000382:microbiology; D014774:Virulence; D037521:Virulence Factors / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D001426:Bacterial Proteins; D004268:DNA-Binding Proteins; D037521:Virulence Factors