Manganese Transport Protein Vital to Lyme Disease Bacteria

As no metal transporter had been identified in Bb, investigators from the University of Texas Southwestern Medical Center (Dallas, USA) set out to find one.

The protein they found, BmtA, lacked homology to any known manganese transporter, so the investigators speculated that BmtA might comprise a novel mechanism for manganese acquisition by a bacterial pathogen. To study how BmtA works the investigators generated a number of mutant strains of Bb that lacked the gene that encodes for it.

They reported in the February 13, 2009, online edition of the journal the Proceedings of the [U.S.] National Academy of Sciences (PNAS) that the mutants grew slightly slower than wild-type Bb in vitro. BmtA mutants were sensitive to the chelating actions of EDTA (ethylenediaminetetraacetic acid), suggesting a role for BmtA in metal utilization. Intracellular accumulation of manganese was substantially diminished in the mutants, indicating that the protein was operative in manganese uptake.

BmtA was found to be essential to the infectious life cycle of Bb in ticks and mammals. In addition, the mutants were sensitive to treatment with t-butyl hydroperoxide, implying that BmtA, and thus manganese, was important to Bb for detoxifying reactive oxygen species, including those potentially liberated by immune effector cells during the innate immune response.

"When you try to grow the mutant strain in a mouse, however, it cannot grow,” said senior author Dr. Michael Norgard, professor of microbiology at the University of Texas Southwestern Medical Center. "The fact that the bacterium without this particular manganese transporter cannot grow in a mouse raises important questions about what aspects of physiology and metabolism contribute to the pathogenicity of the organism. I really think that there is also something to the notion that manganese may regulate the expression of other virulence factors. It could be that manganese has more of an indirect effect, but more research is needed to determine what must happen for B. burgdorfei to become virulent.”

"We believe our findings provide a foundation for further defining metal homeostasis in this human pathogen and may lead to new strategies for thwarting Lyme disease,” said Dr. Norgard.

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University of Texas Southwestern Medical Center