A promoter mutation causes differential nitrate reductase activity of Mycobacterium tuberculosis and Mycobacterium bovis.
The recent publication of the genome sequence of Mycobacterium bovis showed >99.95% identity to M. tuberculosis. No genes unique to M. bovis were found. Instead numerous single-nucleotide polymorphisms (SNPs) were identified. This has led to the hypothesis that differential gene expression due to SNPs might explain the differences between the human and bovine tubercle bacilli. One phenotypic distinction between M. tuberculosis and M. bovis is nitrate reduction, which not only is an essential diagnostic tool but also contributes to mycobacterial pathogenesis. We previously showed that narGHJI encodes a nitrate reductase in both M. tuberculosis and M. bovis and that NarGHJI-mediated nitrate reductase activity was substantially higher in the human tubercle bacillus. In the present study we used a genetic approach to demonstrate that an SNP within the promoter of the nitrate reductase gene cluster narGHJI is responsible for the different nitrate reductase activity of M. tuberculosis and M. bovis. This is the first example of an SNP that leads to differential gene expression between the human and bovine tubercle bacilli.
Stermann
Marion
M
Department of Medical Microbiology and Hospital Epidemiology, Medical School Hannover, Carl-Neuberg-Strasse 1, 30625 Hanover, Germany.
Sedlacek
Ludwig
L
Maass
Silvia
S
Bange
Franz-Christoph
FC
D009154:Mutation; D009163:Mycobacterium bovis / Q000201:enzymology*; D009169:Mycobacterium tuberculosis / Q000201:enzymology*; D050901:Nitrate Reductase; D009565:Nitrate Reductases / Q000235:genetics* / Q000378:metabolism; D009573:Nitrites / Q000378:metabolism; D009876:Operon; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D011995:Recombination, Genetic
D009573:Nitrites; D009565:Nitrate Reductases; D050901:Nitrate Reductase