Emergence and Molecular Characterization of Extensively Drug-Resistant Mycobacterium tuberculosis Clinical Isolates from the Delhi Region in India
Alka Khanna,V. Samuel Raj,Bansidhar Tarai,Ruchi Sood,Pawan Kumar Pareek,Dilip J. Upadhyay,Pawan Sharma,Ashok Rattan,Kulvinder Singh Saini,Harpal Singh +9 more
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TLDR
The data in this report clearly establish the presence of phenotypically distinct XDR strains in India by molecular profiling and further identify specific mutational hot spots within key genes of XDR-TB strains.Abstract:
We screened 194 Mycobacterium tuberculosis strains isolated from tuberculosis (TB) patients in Delhi and neighboring regions in India to identify the prevalence of extensive drug resistance (XDR) in clinical isolates. Among these, 104 isolates were found to be multidrug resistant (MDR), and 6 were identified as XDR isolates, which was later confirmed by antimicrobial susceptibility testing against the respective drug screening panel. Genotyping was carried out by amplifying and sequencing the following genes: rpoB (rifampin), katG (isoniazid), gyrA (fluoroquinolones), and rrs (amikacin, kanamycin, and capreomycin). Our analyses indicated that mutations at the hot spots of these genes were positively correlated with drug resistance in clinical isolates. The key mutation observed for rpoB was in the codon for amino acid position 531 (S531L), and other mutations were seen in the hot spot, including those encoding Q510P, L511H, D516V, and H526Y mutations. We identified S315T and R463L substitutions encoded in the katG locus. An S95T substitution encoded in the gyrA locus was the most common mutation observed in fluoroquinolone-resistant isolates. In addition, we saw D94G and D94N mutations encoded in the QRDR region. The 16S rRNA (rrs) gene encoded mainly the A1401G mutation and an additional mutation, G1484T, resulting in ribosomal modifications. Taken together, the data in this report clearly establish the presence of phenotypically distinct XDR strains in India by molecular profiling and further identify specific mutational hot spots within key genes of XDR-TB strains.read more
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Evaluation of genetic mutations associated with Mycobacterium tuberculosis resistance to amikacin, kanamycin and capreomycin: a systematic review.
Sophia B. Georghiou,Marisa Magaña,Richard S. Garfein,Donald G. Catanzaro,Antonino Catanzaro,Timothy C. Rodwell +5 more
TL;DR: In this article, the authors conducted a systematic review of all published studies evaluating Mtb mutations associated with resistance to AMK, KAN, CAP in order to characterize the diversity and frequency of mutations as well as describe the strength of the association between specific mutations and phenotypic resistance in global populations.
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Resistance to Isoniazid and Ethionamide in Mycobacterium tuberculosis: Genes, Mutations, and Causalities
TL;DR: Each known mechanism of resistance to INH and ETH is described and its importance in M. tuberculosis clinical isolates is described.
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Characterization of Mutations Conferring Extensive Drug Resistance to Mycobacterium tuberculosis Isolates in Pakistan
TL;DR: Additional genetic loci need to be tested for detection of mutations conferring fluoroquinolone, aminoglycoside, and capreomycin resistance in order to improve molecular diagnosis of regional XDR M. tuberculosis strains.
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Incidence and risk factors for extensively drug-resistant tuberculosis in Delhi region.
Chhavi Porwal,Amit Kaushik,Nayani Makkar,Jayant Nagesh Banavaliker,M. Hanif,Rupak Singla,Anuj K. Bhatnagar,Digambar Behera,Pande Jn,Urvashi B. Singh +9 more
TL;DR: A concern about existence of XDR-TB in India, though small, is raised, signaling a need to strengthen the TB control program for early diagnosis of both tuberculosis and drug resistance in order to break the chains of transmission.
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Prevalence of drug-resistant pulmonary tuberculosis in India: systematic review and meta-analysis.
TL;DR: The alarming increase in the trend of anti-TB drug resistance in India warrants the need for a structured nationwide surveillance to assist the National TB Control Program in strengthening treatment strategies for improved outcomes.
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