title: A manganese transporter, BB0219 (BmtA), is required for virulence by the Lyme disease spirochete, Borrelia burgdorferi.
abstract: Borrelia burgdorferi (Bb), the causative agent of Lyme disease, is transmitted to mammalian hosts through an arthropod (tick) vector. To establish infection, Bb must acquire essential nutrients, including transition metals, from its mammalian and tick hosts. Thus far, no metal transporter has been identified in Bb. Here, we report the identification of the first metal transporter, BmtA (BB0219), in Bb. BmtA-deficient mutants of virulent Bb were readily generated, and the mutants grew slightly slower than wild-type Bb in vitro. However, BmtA mutants were sensitive to the chelating actions of EDTA, suggesting a role for BmtA in metal utilization. Intracellular accumulation of manganese (Mn) was substantially diminished in the bmtA mutant, indicating that BmtA was operative in Mn uptake. Given that BmtA lacks homology to any known Mn transporter, we postulate that BmtA is part of a novel mechanism for Mn acquisition by a bacterial pathogen. BmtA also was essential to the infectious life cycle of Bb in ticks and mammals, thereby qualifying BmtA as a new borrelial virulence factor. In addition, the bmtA mutant was sensitive to treatment with t-butyl hydroperoxide, implying that BmtA, and thus Mn, is important to Bb for detoxifying reactive oxygen species, including those potentially liberated by immune effector cells during the innate immune response. Our discovery of the first molecule involved in metal transport in Bb provides a foundation for further elucidating metal homeostasis in this important human pathogen, which may lead to new strategies for thwarting Lyme disease.
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: Ming
authors.initials: M
authors.lastname: He
authors.forename: Tara
authors.initials: T
authors.lastname: Oman
authors.forename: X Frank
authors.initials: XF
authors.lastname: Yang
authors.forename: Michael V
authors.initials: MV
authors.lastname: Norgard
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D025065:Borrelia burgdorferi / Q000235:genetics / Q000378:metabolism* / Q000472:pathogenicity*; D027682:Cation Transport Proteins / Q000235:genetics / Q000378:metabolism*; D003198:Computer Simulation; D008193:Lyme Disease / Q000378:metabolism*; D008345:Manganese / Q000378:metabolism*; D051379:Mice; D005810:Multigene Family / Q000235:genetics; D009154:Mutation / Q000235:genetics; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D027682:Cation Transport Proteins; D017382:Reactive Oxygen Species; D008345:Manganese