Abstract Title:

A manganese transporter, BB0219 (BmtA), is required for virulence by the Lyme disease spirochete, Borrelia burgdorferi.

Abstract Source:

Proc Natl Acad Sci U S A. 2009 Mar 3;106(9):3449-54. Epub 2009 Feb 13. PMID: 19218460

Abstract Author(s):

Zhiming Ouyang, Ming He, Tara Oman, X Frank Yang, Michael V Norgard

Article Affiliation:

Department of Microbiology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.

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.

Study Type : In Vitro Study

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