A Ser315Thr Substitution in KatG Is Predominant in Genetically Heterogeneous Multidrug-Resistant Mycobacterium tuberculosis Isolates Originating from the St. Petersburg Area in Russia

Abstract

Parts of katG and rpoB from 27 RussianMycobacterium tuberculosis isolates were sequenced to detect mutations causing resistance to isoniazid (INH) and rifampin (RMP), respectively. All 24 INH-resistant isolates had a mutatedkatG, and 22 of them (91.7%) carried a mutation coding for a Ser315Thr shift. An rpoB mutation was noted for each of the 21 RMP-resistant isolates, with Ser531Leu being the most prevalent change encoded. Only two isolates had identical IS6110fingerprints.

Genotypic and phenotypic characteristics of tunisian isoniazid-resistant Mycobacterium tuberculosis strains

“…This is in concordance with previous studies in which 12 to 75% of INH-resistant strains contained mutations either in codon 315 of the katG gene or in inhA ribosomal binding site (Rouse et al, 1995;Musser et al, 1996;Marttila et al, 1998).…”

“…Actually, it's thought that this resistance may arise through distinct mutations frequencies in the katG, inhA genes (regulatory and structural regions), oxyR-aphC intergenic region, and kasA (Silva et al, 2003). Although diverse array mutations are uniquely represented among INH resistant strains, amino acid substitutions located at position 315 in katG gene are the most abundant, and in some geographic areas, this mutation was associated with MDR (Dobner et al, 1997;Marttila et al, 1998;Mokrousov et al, 2002a). It was also reported, that most INH-resistant strains carrying katG315 mutation showed a significant decrease in catalase activity associated with high-INH level MICs (van Soolingen et al, 2000;Ramaswamy et al, 2003).…”

Nosocomial Outbreak of Multidrug-Resistant Tuberculosis Caused by a Strain of Mycobacterium tuberculosis W-Beijing Family in St. Petersburg, Russia

“…It is worthy of note that the rpoB531 TCG→TTG (Ser531→Leu) and katG315 AGC→ACC (Ser315→Thr) mutations recognized in the outbreak strain B were previously reported as highly predominant among MDR isolates originating in the St. Petersburg area of Russia in 1993 to 1995 [26]. Recently, we showed a 93.6% prevalence of the katG315ACC mutant allele among 204 isoniazid-resistant Mycobacterium tuberculosis isolates in the area of northwestern Russia, including St. Petersburg [19].…”

Contribution of AGC to ACC and other mutations at codon 315 of the katG gene in isoniazid-resistant Mycobacterium tuberculosis isolates from the Middle East

“…Clinically relevant high level of resistance, however, is mainly due to mutations within the katG gene, particularly involving codon 315 [8,9]. Although a point mutation (AGC to ACC) resulting in Ser315Thr substitution is most common [9][10][11], other mutations involving codon 315 in the katG gene also occur in isoniazid-resistant strains [6][7][8][12][13][14].…”

“…Although a point mutation (AGC to ACC) resulting in Ser315Thr substitution is most common [9][10][11], other mutations involving codon 315 in the katG gene also occur in isoniazid-resistant strains [6][7][8][12][13][14]. The occurrence of ACC and other mutations at codon 315 of the katG gene varies considerably around the world and a high prevalence of ACC mutation has been exploited for developing a rapid molecular screen for the detection of majority of isoniazid-resistant M. tuberculosis isolates from a given geographical location [9,10,12]. The prevalence of AGC to ACC mutation in isoniazid-resistant M. tuberculosis isolates was found to vary from a low of 35% in Beirut (Lebanon) to 65-70% in Kuwait and Dubai (United Arab Emirates, UAE) [15,16].…”