Molecular Characterization and Tree Evolution of Rifampicine and Isoniazid-Resistance in Multi Drug Resistance Strains Isolated From Primary and Secondary Tuberculosis Diseases in Southern Endemic Border of Iran

Study Objective: The aim of this study was to investigate frequency and type of mutations in the katG and rpoB genes and provide tree evolution of M. tuberculosis isolates collected from patients in southern endemic region of Iran.

Setting and Design: 91 sputums were collected from suspected tubercu­losis patients, 34 rifampicine isolates and 26 isoniazid-resistant were iden­tified as M. tuberculosis. Drug susceptibility was determined by using CDC standard conventional proportional method.

Result: 60 mutations and 13 micro deletions were identified in 29 rifampicin resistant M. tuberculosis strains (85%). In 5 rifampicin resistant M. tuberculosis isolates (15%) no mutations were found in the core region of the rpoB gene. Most frequent mutations detected among Iranian strains were in codons 523(58.6%) and 526 (41%). Six alleles in codon 526 and 3 alleles in triplets in each codons 507(27%), 508 (20.5%), 513(10.2%) were found. In 21 isoniazid resistance isolates three types of mutations: AGC--ACC (Ser—>Thr) (80%), AGC^AGG (Ser—Arg) (5%) and AGC^AAC (Ser—Asn) (15%) observed in codon 315. One type of muta­tion was detected in codons 311,299, and 322. Two isolates revealed iso­niazid resistance without demonstrating mutation in katG gene. In con­tract with tree evolution are 2 groups: group A- similar to the standard and Eastern strains (China, Taiwan) and group B- strains of another genotype.

Conclusion: This research demonstrates that codons 315 and 311 are more frequently observed agent indicating resistance to isoniazid and 523,526 for rifampicine resistance and gives a first overview of the M, tuberculosis strains circulating in Iran during the first survey of anti-tuber­culosis drug-resistance.