The pathogenic mycobacteriumMycobacterium tuberculosisencodes two members of the DtxR/MntR family of metalloregulators, IdeR and SirR. IdeR represses gene expression in response to ferrous iron, and we here demonstrate that SirR (Rv2788), although also annotated as an iron-dependent repressor, functions instead as a manganese-dependent transcriptional repressor and is therefore renamed MntR. MntR regulates transporters that promote manganese import and genes that respond to metal ion deficiency such as theesx3system. Repression of manganese import by MntR is essential for survival ofM. tuberculosisunder conditions of high manganese availability, butmntRis dispensable during infection. In contrast, manganese import by MntH and MntABCD was found to be indispensable for replication ofM. tuberculosisin macrophages. These results suggest that manganese is limiting in the host and that interfering with import of this essential metal may be an effective strategy to attenuateM. tuberculosis.
MntR was identified as a transcriptional regulator responsible for maintaining manganese (Mn) homeostasis in Mycobacterium tuberculosis (Mtb). Analysis of the MntR regulon identified new Mn transporters, repressed by MntR and Mn. MntR was dispensable during infection while Mn import was essential for normal replication of Mtb in macrophages, suggesting that Mtb faces Mn limitation in vivo.