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.

[1]  D. Soll,et al.  Occurrence and stability of insertion sequences in Mycobacterium tuberculosis complex strains: evaluation of an insertion sequence-dependent DNA polymorphism as a tool in the epidemiology of tuberculosis , 1991, Journal of clinical microbiology.

[2]  R. Lathigra,et al.  Genetic analysis of superoxide dismutase, the 23 kilodalton antigen of Mycobacterium tuberculosis , 1991, Molecular microbiology.

[3]  J. T. Crawford,et al.  IS6110: conservation of sequence in the Mycobacterium tuberculosis complex and its utilization in DNA fingerprinting. , 1991, Molecular and cellular probes.

[4]  J. Guesdon,et al.  Characterization of a Mycobacterium tuberculosis insertion sequence, IS6110, and its application in diagnosis , 1990, Journal of clinical microbiology.

[5]  Z. F. Zainuddin,et al.  Characterization of a Mycobacterium tuberculosis insertion sequence belonging to the IS3 family , 1990, Molecular microbiology.

[6]  D van Soolingen,et al.  Insertion element IS986 from Mycobacterium tuberculosis: a useful tool for diagnosis and epidemiology of tuberculosis , 1990, Journal of clinical microbiology.

[7]  J. T. Crawford,et al.  IS6110, an IS-like element of Mycobacterium tuberculosis complex , 1990, Nucleic Acids Res..

[8]  Z. F. Zainuddin,et al.  Polymorphic repetitive DNA sequences in Mycobacterium tuberculosis detected with a gene probe from a Mycobacterium fortuitum plasmid. , 1989, Journal of general microbiology.

[9]  K. Mullis,et al.  Primer-directed enzymatic amplification of DNA with a thermostable DNA polymerase. , 1988, Science.

[10]  J. Sambrook,et al.  Molecular Cloning: A Laboratory Manual , 2001 .

[11]  V. Aber,et al.  Virulence and resistance to superoxide, low pH and hydrogen peroxide among strains of Mycobacterium tuberculosis. , 1978, Journal of general microbiology.

[12]  W. Schaefer,et al.  Lipids of Putative Relevance to Virulence in Mycobacterium tuberculosis: Phthiocerol Dimycocerosate and the Attenuation Indicator Lipid , 1974, Infection and immunity.

[13]  G. Diaz,et al.  Acquired isoniazid resistance and catalase activity of myobacteria. , 1968, The American review of respiratory disease.

[14]  D. Mitchison,et al.  VIRULENCE IN THE GUINEA-PIG, SUSCEPTIBILITY TO HYDROGEN PEROXIDE, AND CATALASE ACTIVITY OF ISONIAZID-SENSITIVE TUBERCLE BACILLI FROM SOUTH INDIAN AND BRITISH PATIENTS. , 1963, The Journal of pathology and bacteriology.

[15]  G. Middlebrook.  Isoniazid-resistance and catalase activity of tubercle bacilli; a preliminary report. , 1954, American review of tuberculosis.