Disease relevance of ahpC

• Molecular analysis of isoniazid-resistant Mycobacterium tuberculosis isolates from England and Wales reveals the phylogenetic significance of the ahpC -46A polymorphism [1].
• Using a green fluorescence protein vector (gfp)-ahpC reporter construct we present data showing that repression of ahpC of virulent M. tuberculosis also occurred during growth inside macrophages, whereas derepression in BCG was again seen under identical conditions [2].

High impact information on ahpC

• Compensatory ahpC gene expression in isoniazid-resistant Mycobacterium tuberculosis [3].
• One of the genes affected by oxyR lesions, ahpC (encoding an alkylhydroperoxide reductase) may determine the intrinsic sensitivity of mycobacteria to isoniazid [4].
• The ahpC gene, which encodes a critical subunit of alkyl hydroperoxide reductase, is one of the targets usually controlled by oxyR in bacteria [5].
• In a demonstration of the critical role of ahpC in sensitivity to INH, insertional inactivation of ahpC on the chromosome of Mycobacterium smegmatis, a species naturally insensitive to INH, dramatically increased its susceptibility to this compound [5].
• We have also isolated DNA sequences homologous to oxyR and ahpC from M. tuberculosis and Mycobacterium avium [6].

Chemical compound and disease context of ahpC

• In this work, M. tuberculosis H37Rv and Mycobacterium smegmatis mc(2)155 ahpC knockout mutants were tested for sensitivity to reactive nitrogen intermediates, in particular peroxynitrite, a highly reactive combinatorial product of reactive nitrogen and oxygen species, and sensitivity to bactericidal mechanisms in resting and activated macrophages [7].

Biological context of ahpC

• An increase in minimal inhibitory concentration for isoniazid was observed upon transformation of M. tuberculosis H37Rv with cosmids carrying the oxyR-ahpC region of M. leprae [8].
• These do not include the oxidative stress genes ahpC and sodA, or those for siderophore production [9].
• M. marinum AhpC levels detected by immunoblotting, were increased upon treatment with H2O2, in keeping with the presence of a functional OxyR and its binding site within the promoter region of ahpC [10].
• In 9/10 isolates, mutations in the ahpC promoter region were located in the 105 bp oxyR-ahpC intergenic region [11].
• To initiate investigations of the regulation of oxidative stress in mycobacteria and consequences of the elimination of oxyR in M. tuberculosis, in this work we tested the hypothesis that mycobacterial OxyR acts as a DNA binding protein and analyzed its interactions with the oxyR and ahpC promoters [12].

Associations of ahpC with chemical compounds

• Mutations in katG, ahpC, and inhA were associated with rifampin resistance, but only katG315 mutations were associated with ethambutol resistance [13].
• DESIGN: M. bovis ATCC35723 was electroporated with linear fragments of deoxyribonucleic acid (DNA) containing an ahpC gene interrupted by a kanamycin resistance gene [14].

Analytical, diagnostic and therapeutic context of ahpC

• The katG, inhA and ahpC genes, in 71 isoniazid (INH)-resistant and 26 INH-susceptible Mycobacterium tuberculosis isolates, from South Korea were examined by sequencing and MspI restriction enzyme analysis [15].

References