title: On the catalase-peroxidase gene, katG, of Mycobacterium leprae and the implications for treatment of leprosy with isoniazid.
abstract: The toxicity of the potent tuberculocidal agent, isoniazid, is mediated by the heme-containing enzyme, catalase-peroxidase, encoded by the katG gene. Although isoniazid has been used for the treatment of leprosy, it is shown here that the katG gene of Mycobacterium leprae is a pseudogene, which has probably been inactivated by multiple mutations. Inactive genes were detected by the polymerase chain reaction in several isolates of M. leprae, of different geographical origins, and attempts to complement an isoniazid-resistant strain of Mycobacterium smegmatis with the katG pseudogene were unsuccessful. Isoniazid is thus likely to be of no therapeutic benefit to leprosy patients.
authors.affiliation: Unité de Génétique Moléculaire Bactérienne, Institut Pasteur, Paris, France.
authors.forename: K
authors.initials: K
authors.lastname: Eiglmeier
authors.forename: H
authors.initials: H
authors.lastname: Fsihi
authors.forename: B
authors.initials: B
authors.lastname: Heym
authors.forename: S T
authors.initials: ST
authors.lastname: Cole
mesh_terms: D000995:Antitubercular Agents / Q000494:pharmacology*; D001426:Bacterial Proteins; D003001:Cloning, Molecular; D003360:Cosmids; D005798:Genes, Bacterial / Q000235:genetics; D007538:Isoniazid / Q000494:pharmacology*; D007918:Leprosy / Q000188:drug therapy / Q000382:microbiology*; D008969:Molecular Sequence Data; D009166:Mycobacterium leprae / Q000187:drug effects / Q000201:enzymology / Q000235:genetics*; D010544:Peroxidases / Q000235:genetics*; D011544:Pseudogenes / Q000235:genetics; D017386:Sequence Homology, Amino Acid
chemical_list: D000995:Antitubercular Agents; D001426:Bacterial Proteins; D010544:Peroxidases; C076136:catalase HPI; D007538:Isoniazid