Peroxiredoxin systems in mycobacteria.
Like other actinomycetes Mycobacterium tuberculosis lacks glutathione and, consequently, the glutathione peroxidases that dominate the antioxidant defence of its mammalian hosts. The hydrogen peroxide metabolism of the pathogen has for long been recognised to depend on a heme-containing catalase/peroxidase. Clinical isolates lacking the catalase were virulent and proved to be resistant to the first line tuberculostatic isoniazid, because the enzyme is evidently required to activate this drug. The survival and virulence of such strains are attributed to the peroxiredoxin-type peroxidases alkyl hydroperoxide reductase (AhpC) and thioredoxin peroxidase (TPx). The most common AhpC reductant in bacteria, the disulfide reductase AhpF, is deleted in M. tuberculosis. Instead, AhpC can be reduced by AhpD, a CXXC-motif-containing protein, or by one of the mycobacterial thioredoxins, TrxC. TPx is reduced by thioredoxins B and C. Mycobacteria contain three more peroxiredoxins, the 1-Cys-Prx AhpE, Bcp and BcpB, whose function and reductants are still unknown.
Jaeger
Timo
T
MOLISA GmbH, Molecular Links Sachsen-Anhalt, Magdeburg, Germany.
D020816:Amino Acid Motifs / Q000502:physiology; D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D000995:Antitubercular Agents / Q000494:pharmacology / Q000627:therapeutic use; D001426:Bacterial Proteins / Q000378:metabolism*; D002374:Catalase; D024881:Drug Resistance, Bacterial / Q000187:drug effects / Q000502:physiology*; D005978:Glutathione; D005979:Glutathione Peroxidase; D006861:Hydrogen Peroxide; D007538:Isoniazid / Q000494:pharmacology / Q000627:therapeutic use; D008322:Mammals / Q000378:metabolism; D009169:Mycobacterium tuberculosis / Q000201:enzymology* / Q000472:pathogenicity; D010084:Oxidation-Reduction; D054464:Peroxiredoxins / Q000378:metabolism*; D013879:Thioredoxins / Q000378:metabolism*; D014376:Tuberculosis / Q000188:drug therapy / Q000201:enzymology
D000975:Antioxidants; D000995:Antitubercular Agents; D001426:Bacterial Proteins; D013879:Thioredoxins; D006861:Hydrogen Peroxide; D054464:Peroxiredoxins; D002374:Catalase; D005979:Glutathione Peroxidase; D005978:Glutathione; D007538:Isoniazid