Gert van der Hoek
In Memoriam - Editor, Senior Moderator
Emergence of Extensive Drug Resistant (XDR) Mycobacterium Tuberculosis and Molecular Characterization of these clinical isolates from Delhi Region, India.
Antimicrob Agents Chemother. 2010 Aug 16
Abstract
We have screened 194 Mycobacterium tuberculosis strains isolated from the TB patients of Delhi and neighboring region to identify the prevalence of extensive drug resistance (XDR) in clinical isolates.
Out of these, one hundred four isolates were found to be multidrug resistant (MDR), 6 were identified as XDR isolates, which were later confirmed with antimicrobial susceptibility testing against respective drug screening panel.
The genotyping was carried out by amplifying and sequencing the following genes: rpoB (rifampin), katG (isoniazid), gyrA (fluoroquinolones), and rrs (AMK, KAN, CAP). Our analyses indicated that the mutations at the hotspot of these genes were positively correlated with the drug resistance in clinical isolates.
The key mutation observed in rpoB was at the amino acid position 531 (S531L) and other mutations were seen in the hotspot Q510P, L511H, D516V and H526Y.
We identified S315T and R463L substitution in the katG locus. A S95T substitution in the gyrA locus was the most common mutation observed in fluoroquinolone resistant isolates.
In addition, we have seen the mutations at D94G or D94N in the QRDR region. The 16S rRNA rrs exhibited mutation mainly at A1401G and an additional mutation at G1484T, resulting in ribosomal modifications.
Taken together, this report has clearly established the presence of phenotypically distinct XDR strains in India with their molecular profiling, and further identifying specific mutational hot spots within key genes of XDR-TB strains.
http://www.ncbi.nlm.nih.gov/pubmed/20713679
Antimicrob Agents Chemother. 2010 Aug 16
Abstract
We have screened 194 Mycobacterium tuberculosis strains isolated from the TB patients of Delhi and neighboring region to identify the prevalence of extensive drug resistance (XDR) in clinical isolates.
Out of these, one hundred four isolates were found to be multidrug resistant (MDR), 6 were identified as XDR isolates, which were later confirmed with antimicrobial susceptibility testing against respective drug screening panel.
The genotyping was carried out by amplifying and sequencing the following genes: rpoB (rifampin), katG (isoniazid), gyrA (fluoroquinolones), and rrs (AMK, KAN, CAP). Our analyses indicated that the mutations at the hotspot of these genes were positively correlated with the drug resistance in clinical isolates.
The key mutation observed in rpoB was at the amino acid position 531 (S531L) and other mutations were seen in the hotspot Q510P, L511H, D516V and H526Y.
We identified S315T and R463L substitution in the katG locus. A S95T substitution in the gyrA locus was the most common mutation observed in fluoroquinolone resistant isolates.
In addition, we have seen the mutations at D94G or D94N in the QRDR region. The 16S rRNA rrs exhibited mutation mainly at A1401G and an additional mutation at G1484T, resulting in ribosomal modifications.
Taken together, this report has clearly established the presence of phenotypically distinct XDR strains in India with their molecular profiling, and further identifying specific mutational hot spots within key genes of XDR-TB strains.
http://www.ncbi.nlm.nih.gov/pubmed/20713679