Deletion of the putative antioxidant noxR1 does not alter the virulence ofMycobacterium tuberculosis H37Rv

Setting: The cloned M. tuberculosis noxR1 gene has been shown to confer res istance to reactive nitrogen intermediates (RNI) and reactive oxygen interm ediates (ROI) upon Escherichia coil and Mycobacterium smegmatis. Objective: To investigate the role of noxR1 in resistance to RNI and virule nce of M. tuberculosis. Design: The noxR1 gene was deleted from M. bovis BCG and M. tuberculosis H3 7Rv by allelic exchange. The mutants were compared to wild type strains wit h respect to resistance to chemically generated RNI. The virulence of the M . tuberculosis mutant was investigated in a murine model of infection. Results: The NoxR1 mutants grew normally in Sautons and 7H9 broths. The BCG mutant demonstrated decreased resistance to in vitro generated RNI compare d to the wild type. Resistance to RNI could be restored to the mutant by re introduction of the noxR1 locus on a replicating plasmid. However, deletion of noxR1 from M. tuberculosis H37Rv did not result in decreased resistance to RN1 nor a difference in growth and survival of the bacterium during mur ine infection. Conclusion: The noxR1 gene locus in M. bovis BCG bestows ability to resist RNI generated in vitro. In M. tuberculosis H37Rv, however, noxR1 is either not involved in RNI resistance and virulence or is better compensated for b y other mechanisms. (C) 2000 Harcourt Publishers Ltd.