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Gene Review

ahpC  -  alkyl hydroperoxide reductase

Mycobacterium tuberculosis CDC1551

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Disease relevance of ahpC

  • Mutations to the regulatory region of the ahpC gene, resulting in overproduction of alkyl hydroperoxide reductase, were encountered frequently in a large collection of isoniazid (INH)-resistant clinical isolates of Mycobacterium tuberculosis but not in INH-susceptible strains [1].
  • Monospecific rabbit antiserum against AhpC and AhpD reacted with 9 strains of M. avium subsp. paratuberculosis but not with 20 other mycobacterial strains except for a Mycobacterium gordonae strain, against which a weak cross-reactive band was produced [2].

High impact information on ahpC

  • Mutations in katG, ahpC, and inhA were associated with rifampin resistance, but only katG315 mutations were associated with ethambutol resistance [3].
  • Restoration of virulence was not seen in an INH-resistant M. tuberculosis strain that overexpressed ahpC, and this finding was confirmed by experiments performed with appropriate M. bovis strains in guinea pigs [1].
  • Surprisingly, most INH-resistant strains with KatG codon 315 substitutions that substantially reduce catalase-peroxidase activity and confer high MICs of INH lacked alterations in the ahpC gene or oxyR-ahpC intervening region [4].
  • Transformation of the INH-susceptible reference strain, M. tuberculosis H37Rv, with plasmids bearing the ahpC genes of M. tuberculosis or M. leprae did not result in a significant increase in the MIC [1].
  • The ahpC compensatory mutations are apparently uncommon because strains with a KatG null phenotype are relatively rare among epidemiologically independent INH-resistant organisms [4].

Chemical compound and disease context of ahpC

  • Oxidative stress response and its role in sensitivity to isoniazid in mycobacteria: characterization and inducibility of ahpC by peroxides in Mycobacterium smegmatis and lack of expression in M. aurum and M. tuberculosis [5].

Associations of ahpC with chemical compounds

  • Two highly INH-resistant mutants of H37Rv, BH3 and BH8, were isolated in vitro and shown to produce no or little KatG activity and, in the case of BH3, to overproduce alkyl hydroperoxide reductase as the result of an ahpC regulatory mutation that was also found in some clinical isolates [1].
  • M. bovis with an up-regulated ahpC gene was more resistant to cumene hydroperoxide than its parent strain, which had a wild-type ahpC promoter [6].


  1. Effects of overexpression of the alkyl hydroperoxide reductase AhpC on the virulence and isoniazid resistance of Mycobacterium tuberculosis. Heym, B., Stavropoulos, E., Honoré, N., Domenech, P., Saint-Joanis, B., Wilson, T.M., Collins, D.M., Colston, M.J., Cole, S.T. Infect. Immun. (1997) [Pubmed]
  2. Alkyl hydroperoxide reductases C and D are major antigens constitutively expressed by Mycobacterium avium subsp. paratuberculosis. Olsen, I., Reitan, L.J., Holstad, G., Wiker, H.G. Infect. Immun. (2000) [Pubmed]
  3. Population genetics study of isoniazid resistance mutations and evolution of multidrug-resistant Mycobacterium tuberculosis. Hazbón, M.H., Brimacombe, M., Bobadilla del Valle, M., Cavatore, M., Guerrero, M.I., Varma-Basil, M., Billman-Jacobe, H., Lavender, C., Fyfe, J., García-García, L., León, C.I., Bose, M., Chaves, F., Murray, M., Eisenach, K.D., Sifuentes-Osornio, J., Cave, M.D., Ponce de León, A., Alland, D. Antimicrob. Agents Chemother. (2006) [Pubmed]
  4. Analysis of the oxyR-ahpC region in isoniazid-resistant and -susceptible Mycobacterium tuberculosis complex organisms recovered from diseased humans and animals in diverse localities. Sreevatsan, S., Pan, X., Zhang, Y., Deretic, V., Musser, J.M. Antimicrob. Agents Chemother. (1997) [Pubmed]
  5. Oxidative stress response and its role in sensitivity to isoniazid in mycobacteria: characterization and inducibility of ahpC by peroxides in Mycobacterium smegmatis and lack of expression in M. aurum and M. tuberculosis. Dhandayuthapani, S., Zhang, Y., Mudd, M.H., Deretic, V. J. Bacteriol. (1996) [Pubmed]
  6. Antisense RNA to ahpC, an oxidative stress defence gene involved in isoniazid resistance, indicates that AhpC of Mycobacterium bovis has virulence properties. Wilson, T., de Lisle, G.W., Marcinkeviciene, J.A., Blanchard, J.S., Collins, D.M. Microbiology (Reading, Engl.) (1998) [Pubmed]
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