Frequency of rrs and rpsL mutations in streptomycin-resistant Mycobacterium tuberculosis isolates from Iranian patients.

Abstract

Streptomycin (SM) is one of the most effective drugs for the treatment of multidrug-resistant (MDR) tuberculosis. However, resistance to SM is increasingly reported, mainly due to mutations in the rpsL and rrs genes. This study was designed with the aim of determining the nature of SM resistance and the type and frequency of rpsL and rrs mutations among SM-resistant Mycobacterium tuberculosis (MTB) isolates from Iran. A total of 100 clinical monoresistant and MDR MTB isolates were subjected to drug susceptibility testing (DST) for SM. SM-resistant isolates were genotyped by MIRU-VNTR typing. Fragments of the rpsL and rrs genes were amplified to investigate the most common mutations, with subsequent sequence analysis. By DST, 32 isolates (32%) were identified as SM-resistant, of which 50% (16/32) were MDR. By MIRU-VNTR typing, the SM-resistant isolates were classified into 20 different MIRU types and 8 clusters, with Beijing (22%) being the most prevalent genotype. Mutations in the rrs and rpsL genes were identified in 14 (44%) and 10 (31%) of the 32 SM-resistant isolates, respectively. The most common mutations were at rpsL nucleotide 128 (AAG→AGG, Lys43Arg), found in 7 SM-resistant isolates (22%) and nucleotide 263 (A→G, Lys88Arg) in 3 SM-resistant isolates (9%). The results suggest an association between rpsL mutation and SM-resistant strains of Beijing genotype. The existence of SM resistance in 25% of isolates without mutation in rrs and rpsL suggests the occurrence of further mechanisms associated with SM resistance in these isolates.