Alterations in the superoxide dismutase gene of an isoniazid-resistant strain of Mycobacterium tuberculosis.
Genetic analysis of a set of six Mycobacterium tuberculosis strains differing in virulence for the guinea pig revealed an altered restriction enzyme fragmentation pattern associated with the superoxide dismutase (SOD) gene in a low-virulence, isoniazid-resistant strain. In addition, it was found that the SOD enzyme produced by the isoniazid-resistant strain differed in its electrophoretic mobility from the SOD of other M. tuberculosis strains. Detailed analysis of these strain-specific differences showed that the restriction fragment length polymorphism resulted from the presence of a copy of a repetitive element 552 bp upstream of the SOD gene and that the anomalous electrophoretic mobility arose from a single nucleotide change, resulting in replacement of an aspartic acid residue by histidine in the SOD enzyme of the isoniazid-resistant strain. Possible relationships between genetic changes and strain-dependent differences in virulence are discussed.
Zhang
Y
Y
MRC Tuberculosis and Related Infections Unit, Royal Postgraduate Medical School, Hammersmith Hospital, London, United Kingdom.
Garcia
M J
MJ
Lathigra
R
R
Allen
B
B
Moreno
C
C
van Embden
J D
JD
Young
D
D
D000818:Animals; D001483:Base Sequence; D004352:Drug Resistance, Microbial; D005798:Genes, Bacterial; D006168:Guinea Pigs; D007538:Isoniazid / Q000494:pharmacology*; D008969:Molecular Sequence Data; D009154:Mutation; D009169:Mycobacterium tuberculosis / Q000187:drug effects / Q000201:enzymology* / Q000235:genetics; D013482:Superoxide Dismutase / Q000235:genetics*
D013482:Superoxide Dismutase; D007538:Isoniazid