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.