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

Abstract

Setting: The cloned M. tuberculosis noxR1 gene has been shown to confer resistance to reactive nitrogen intermediates (RNI) and reactive oxygen intermediates (ROI) upon Escherichia coli and Mycobacterium smegmatis.

Objective: To investigate the role of noxR1 in resistance to RNI and virulence of M. tuberculosis.

Design: The noxR1 gene was deleted from M. bovis BCG and M. tuberculosis H37Rv by allelic exchange. The mutants were compared to wild type strains with 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 compared to the wild type. Resistance to RNI could be restored to the mutant by reintroduction of the noxR1 locus on a replicating plasmid. However, deletion of noxR1 from M. tuberculosis H37Rv did not result in decreased resistance to RNI nor a difference in growth and survival of the bacterium during murine 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 by other mechanisms.