TY - JOUR
T1 - M. tuberculosis Central Assian Strain 1 MDR isolates have more mutations in rpoB and katG genes compared with other genotypes
AU - Ali, Asho
AU - Hasan, Zahra
AU - Moatter, Tariq
AU - Tanveer, Mahnaz
AU - Hasan, Rumina
N1 - Funding Information:
This study was supported through grants from: The University Research Council, The Aga Khan University, Karachi, Pakistan; Benenden Healthcare Society, UK, and in part through a grant from the Joint Pakistan-U.S. Academic and Research Program HEC/MoST/USAID. We would also like to thank the faculty and staff of the Clinical Microbiology Laboratory and Juma Research Laboratory of the Aga Khan University Hospital, Karachi for their support and help in this study.
PY - 2009
Y1 - 2009
N2 - Pakistan ranks eighth globally among TB burden countries, with a MDR rate of 2-5%. The most prevalent MTB genotype is Central Asian Strain1 (CAS1) followed by the Beijing genogroup. We investigated common mutations in multidrug resistance encoding genes rpoB, katG and inhA of CAS1 and Beijing strains using DNA sequencing and fluorescent resonance energy transfer (FRET) probe based real-time PCR methods. 30 CAS1, 12 Beijing and 20 unclustered spoligotypes, and 10 susceptible MTB strains were tested. The most common mutations in the rpoB gene were at codons 531 (60%), 526 (23%) and 516 (5%). CAS1 strains had a higher frequency of mutations at codon 526 (p<0.001), with more concurrent mutations (p<0.05) compared with Beijing and orphan types. Mutations at codon 315 of the katG gene were higher in CAS1 than Beijing strains (p=0.052). Only 1/62 MDR strain, which belonged to CAS1, had a mutation in the inhA gene. Sensitivity and specificity of probe based assay was 93% and 100% for rpoB, and 95% and 100% for katG, respectively. The FRET probes method detected 84% and 60% of rpoB and katG mutations and can therefore be used as a rapid method of screening MTB strains including CAS1.
AB - Pakistan ranks eighth globally among TB burden countries, with a MDR rate of 2-5%. The most prevalent MTB genotype is Central Asian Strain1 (CAS1) followed by the Beijing genogroup. We investigated common mutations in multidrug resistance encoding genes rpoB, katG and inhA of CAS1 and Beijing strains using DNA sequencing and fluorescent resonance energy transfer (FRET) probe based real-time PCR methods. 30 CAS1, 12 Beijing and 20 unclustered spoligotypes, and 10 susceptible MTB strains were tested. The most common mutations in the rpoB gene were at codons 531 (60%), 526 (23%) and 516 (5%). CAS1 strains had a higher frequency of mutations at codon 526 (p<0.001), with more concurrent mutations (p<0.05) compared with Beijing and orphan types. Mutations at codon 315 of the katG gene were higher in CAS1 than Beijing strains (p=0.052). Only 1/62 MDR strain, which belonged to CAS1, had a mutation in the inhA gene. Sensitivity and specificity of probe based assay was 93% and 100% for rpoB, and 95% and 100% for katG, respectively. The FRET probes method detected 84% and 60% of rpoB and katG mutations and can therefore be used as a rapid method of screening MTB strains including CAS1.
UR - https://www.scopus.com/pages/publications/58049202242
U2 - 10.1080/00365540802570519
DO - 10.1080/00365540802570519
M3 - Article
C2 - 19012077
AN - SCOPUS:58049202242
SN - 0036-5548
VL - 41
SP - 37
EP - 44
JO - Scandinavian Journal of Infectious Diseases
JF - Scandinavian Journal of Infectious Diseases
IS - 1
ER -
