title: Manganese and zinc regulate virulence determinants in Borrelia burgdorferi.
abstract: Borrelia burgdorferi, the causative agent of Lyme disease, must adapt to two diverse niches, an arthropod vector and a mammalian host. RpoS, an alternative sigma factor, plays a central role in spirochetal adaptation to the mammalian host by governing expression of many genes important for mammalian infection. B. burgdorferi is known to be unique in metal utilization, and little is known of the role of biologically available metals in B. burgdorferi. Here, we identified two transition metal ions, manganese (Mn(2+)) and zinc (Zn(2+)), that influenced regulation of RpoS. The intracellular Mn(2+) level fluctuated approximately 20-fold under different conditions and inversely correlated with levels of RpoS and the major virulence factor OspC. Furthermore, an increase in intracellular Mn(2+) repressed temperature-dependent induction of RpoS and OspC; this repression was overcome by an excess of Zn(2+). Conversely, a decrease of intracellular Mn(2+) by deletion of the Mn(2+) transporter gene, bmtA, resulted in elevated levels of RpoS and OspC. Mn(2+) affected RpoS through BosR, a Fur family homolog that is required for rpoS expression: elevated intracellular Mn(2+) levels greatly reduced the level of BosR protein but not the level of bosR mRNA. Thus, Mn(2+) and Zn(2+) appeared to be important in modulation of the RpoS pathway that is essential to the life cycle of the Lyme disease spirochete. This finding supports the emerging notion that transition metals such as Mn(2+) and Zn(2+) play a critical role in regulation of virulence in bacteria.
authors.affiliation: Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, Indiana, USA.
authors.forename: Bryan
authors.initials: B
authors.lastname: Troxell
authors.forename: Meiping
authors.initials: M
authors.lastname: Ye
authors.forename: Youyun
authors.initials: Y
authors.lastname: Yang
authors.forename: Sebastian E
authors.initials: SE
authors.lastname: Carrasco
authors.forename: Yongliang
authors.initials: Y
authors.lastname: Lou
authors.forename: X Frank
authors.initials: XF
authors.lastname: Yang
mesh_terms: D000942:Antigens, Bacterial / Q000096:biosynthesis; D001425:Bacterial Outer Membrane Proteins / Q000096:biosynthesis; D001426:Bacterial Proteins / Q000096:biosynthesis; D025065:Borrelia burgdorferi / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity*; D015964:Gene Expression Regulation, Bacterial / Q000502:physiology*; D015151:Immunoblotting; D008345:Manganese / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012808:Sigma Factor / Q000096:biosynthesis; D014774:Virulence / Q000502:physiology; D037521:Virulence Factors / Q000378:metabolism; D015032:Zinc / Q000378:metabolism*
chemical_list: D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; C079616:OspC protein; D012808:Sigma Factor; D037521:Virulence Factors; C069567:sigma factor KatF protein, Bacteria; D008345:Manganese; D015032:Zinc