Disruption of the Gene Homologous to MammalianNramp1inMycobacterium tuberculosisDoes Not Affect Virulence in Mice

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Abstract
Natural-resistance-associated macrophage protein 1 (Nramp1) is a divalent cation transporter belonging to a family of transporter proteins highly conserved in eukaryotes and prokaryotes. Mammalian and bacterial transporters may compete for essential metal ions during mycobacterial infections. The mycobacterialNramphomolog may therefore be involved inMycobacterium tuberculosisvirulence. Here, we investigated this possibility by inactivating theM. tuberculosis Nramp1gene (Mramp) by allelic exchange mutagenesis. Disruption ofMrampdid not affect the extracellular growth of bacteria under standard conditions. However, theMrampmutation was associated with growth impairment under conditions of limited iron availability. TheMrampmutant displayed no impairment of growth or survival in macrophages derived from mouse bone marrow or inNramp1+/+andNramp1−/−congenic murine macrophage cell lines. Following intravenous challenge in BALB/c mice, counts of parental andMrampmutant strains were similar in the lungs and spleens of the animals at all time points studied. These results indicate thatMrampdoes not contribute to the virulence ofM. tuberculosisin mice.