INHIBITION OF ALKYL HYDROPEROXIDE REDUCTASE, SUBUNIT C (AhpC) TO IMPART SUSCEPTIBILITY TO ANTIMICROBIAL REACTIVE NITROGEN INTERMEDIATES

摘要

The present invention relates to the use of alkyl hydroperoxide reductase subunit C (AhpC) proteins or polypeptides to confer resistance against antimicrobial reactive nitrogen intermediates (RNI). Also disclosed is a DNA molecule encoding alkyl hydroperoxide reductase subunit C from Mycobacterium tuberculosis and conferring on Mycobacterium tuberculosis resistance to antimicrobial RNI. Such DNA encoding AhpC can be used to screen for drugs that inhibit the ability of AhpC to confer resistance to antimicrobial RNI. Such drugs can be used to treat tuberculosis by sensitizing M. tuberculosis to RNI produced by host cells or delivered therapeutically by inhalation or by oral or other parenteral routes. Alternatively, therapeutics can be developed to treat gastric infection. The protein encoded by this DNA molecule is useful in vaccines to prevent infection by Mycobacterium tuberculosis, while the antibodies raised against this protein can be employed in passively immunizing those already infected by the organism. These proteins, antibodies, and DNA molecules may be utilized in diagnostic assays to detect Mycobacterium tuberculosis in tissue or bodily fluids. The protein or polypeptide is also useful as a therapeutic in treating conditions mediated by the production of reactive nitrogen intermediates.