MntR(Rv2788): a transcriptional regulator that controls manganese homeostasis in Mycobacterium tuberculosis.
The pathogenic mycobacterium Mycobacterium tuberculosis encodes 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 the esx3 system. Repression of manganese import by MntR is essential for survival of M. tuberculosis under conditions of high manganese availability, but mntR is dispensable during infection. In contrast, manganese import by MntH and MntABCD was found to be indispensable for replication of M. tuberculosis in 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 attenuate M. tuberculosis.
Public Health Research Institute at New Jersey Medical School, Rutgers State University of New Jersey, 225 Warren Street, Newark, NJ, 07103, USA.
Ruchi
R
Pandey
New Jersey Medical School, Rutgers State University of New Jersey, 185 South Orange Avenue, Newark, NJ, 07103, USA.
Riccardo
R
Russo
Genomics Research Program, NJMS, Rutgers State University of New Jersey, 185 South Orange Avenue, Newark, NJ, USA.
Saleena
S
Ghanny
Department of Microbiology, Cornell University, Ithaca, NY, 14853-8101, USA.
Xiaojuan
X
Huang
Department of Microbiology, Cornell University, Ithaca, NY, 14853-8101, USA.
John
J
Helmann
Public Health Research Institute at New Jersey Medical School, Rutgers State University of New Jersey, 225 Warren Street, Newark, NJ, 07103, USA.
G Marcela
GM
Rodriguez
D000595:Amino Acid Sequence; D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism*; D001483:Base Sequence; D027682:Cation Transport Proteins / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics; D015964:Gene Expression Regulation, Bacterial; D017930:Genes, Reporter; D006706:Homeostasis; D006801:Humans; D008264:Macrophages / Q000382:microbiology; D008345:Manganese / Q000378:metabolism*; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D009154:Mutation; D009169:Mycobacterium tuberculosis / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*
D001426:Bacterial Proteins; D027682:Cation Transport Proteins; D004268:DNA-Binding Proteins; D026901:Membrane Transport Proteins; C433793:MntH protein, bacteria; C433792:MntR protein, bacteria; D012097:Repressor Proteins; D008345:Manganese