scholarly journals Emergence and Molecular Characterization of Extensively Drug-Resistant Mycobacterium tuberculosis Clinical Isolates from the Delhi Region in India

2010 ◽  
Vol 54 (11) ◽  
pp. 4789-4793 ◽  
Author(s):  
Alka Khanna ◽  
V. Samuel Raj ◽  
Bansidhar Tarai ◽  
Ruchi Sood ◽  
Pawan Kumar Pareek ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Mycobacterium Tuberculosis ◽  
Hot Spots ◽  
Hot Spot ◽  
Amino Acid Position ◽  
Multidrug Resistant ◽  
Clinical Isolates ◽  
Common Mutation ◽  
Extensive Drug Resistance

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.

scholarly journals Characterization of Mutations Conferring Extensive Drug Resistance to Mycobacterium tuberculosis Isolates in Pakistan

2011 ◽  
Vol 55 (12) ◽  
pp. 5654-5659 ◽  
Author(s):  
Asho Ali ◽  
Rumina Hasan ◽  
Kauser Jabeen ◽  
Nusrat Jabeen ◽  
Ejaz Qadeer ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Mycobacterium Tuberculosis ◽  
Hot Spot ◽  
East African ◽  
Content Type ◽  
Diagnostic Assays ◽  
Asian Strain ◽  
Central Asian ◽  
Extensive Drug Resistance ◽  
Detection Of Mutations

ABSTRACTThe increasing incidence of extensively drug-resistant (XDR)Mycobacterium tuberculosisin high-tuberculosis-burden countries further highlights the need for improved rapid diagnostic assays. An increasing incidence of XDRM. tuberculosisstrains in Pakistan has been reported, but drug resistance-associated mutations in these strains have not been evaluated previously. We sequenced the “hot-spot” regions ofrpoB,katG,inhA,ahpC,gyrA,gyrB, andrrsgenes in 50 XDRM. tuberculosisstrains. It was observed that 2% of rifampin, 6% of isoniazid, 24% of fluoroquinolone, and 32% of aminoglycoside/capreomycin resistance in XDRM. tuberculosisstrains would be undetected if only these common hot-spot regions were tested. The frequencies of resistance-conferring mutations were found to be comparable among all XDRM. tuberculosisstrain families present, including the Central Asian Strain, Beijing, and East African Indian genogroups and the Unique isolates. 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 XDRM. tuberculosisstrains.

scholarly journals Effect of Mutation and Genetic Background on Drug Resistance in Mycobacterium tuberculosis

2012 ◽  
Vol 56 (6) ◽  
pp. 3047-3053 ◽  
Author(s):  
Lukas Fenner ◽  
Matthias Egger ◽  
Thomas Bodmer ◽  
Ekkehardt Altpeter ◽  
Marcel Zwahlen ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Mycobacterium Tuberculosis ◽  
Hot Spot ◽  
Multidrug Resistant ◽  
Beijing Genotype ◽  
Drug Resistant ◽  
Resistance Mutations ◽  
Content Type ◽  
Drug Resistance Mutations ◽  
Resistant Strains

ABSTRACTBacterial factors may contribute to the global emergence and spread of drug-resistant tuberculosis (TB). Only a few studies have reported on the interactions between different bacterial factors. We studied drug-resistantMycobacterium tuberculosisisolates from a nationwide study conducted from 2000 to 2008 in Switzerland. We determined quantitative drug resistance levels of first-line drugs by using Bactec MGIT-960 and drug resistance genotypes by sequencing the hot-spot regions of the relevant genes. We determined recent transmission by molecular methods and collected clinical data. Overall, we analyzed 158 isolates that were resistant to isoniazid, rifampin, or ethambutol, 48 (30.4%) of which were multidrug resistant. Among 154 isoniazid-resistant strains,katGmutations were associated with high-level andinhApromoter mutations with low-level drug resistance. OnlykatG(S315T) (65.6% of all isoniazid-resistant strains) andinhApromoter −15C/T (22.7%) were found in molecular clusters.M. tuberculosislineage 2 (includes Beijing genotype) was associated with any drug resistance (adjusted odds ratio [OR], 3.0; 95% confidence interval [CI], 1.7 to 5.6;P< 0.0001). Lineage 1 was associated withinhApromoter −15C/T mutations (OR, 6.4; 95% CI, 2.0 to 20.7;P= 0.002). We found that the genetic strain background influences the level of isoniazid resistance conveyed by particular mutations (interaction tests of drug resistance mutations across all lineages;P< 0.0001). In conclusion,M. tuberculosisdrug resistance mutations were associated with various levels of drug resistance and transmission, andM. tuberculosislineages were associated with particular drug resistance-conferring mutations and phenotypic drug resistance. Our study also supports a role for epistatic interactions between different drug resistance mutations and strain genetic backgrounds inM. tuberculosisdrug resistance.

scholarly journals Molecular Characterization of Multidrug-Resistant Isolates of Mycobacterium tuberculosis from Patients in North India

2002 ◽  
Vol 46 (2) ◽  
pp. 443-450 ◽  
Author(s):  
Noman Siddiqi ◽  
Mohammed Shamim ◽  
Seema Hussain ◽  
Rakesh Kumar Choudhary ◽  
Niyaz Ahmed ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Multidrug Resistance ◽  
Binding Site ◽  
Hot Spot ◽  
Multidrug Resistant ◽  
North India ◽  
World Health ◽  
Silent Mutation ◽  
Common Mutation ◽  
Ribosomal Binding Site

ABSTRACT The World Health Organization has identified India as a major hot-spot region for Mycobacterium tuberculosis infection. We have characterized the sequences of the loci associated with multidrug resistance in 126 clinical isolates of M. tuberculosis from India to identify the respective mutations. The loci selected were rpoB (rifampin), katG and the ribosomal binding site of inhA (isoniazid), gyrA and gyrB (ofloxacin), and rpsL and rrs (streptomycin). We found known as well as novel mutations at these loci. Few of the mutations at the rpoB locus could be correlated with the drug resistance levels exhibited by the M. tuberculosis isolates and occurred with frequencies different from those reported earlier. Missense mutations at codons 526 to 531 seemed to be crucial in conferring a high degree of resistance to rifampin. We identified a common Arg463Leu substitution in the katG locus and certain novel insertions and deletions. Mutations were also mapped in the ribosomal binding site of the inhA gene. A Ser95Thr substitution in the gyrA locus was the most common mutation observed in ofloxacin-resistant isolates. A few isolates showed other mutations in this locus. Seven streptomycin-resistant isolates had a silent mutation at the lysine residue at position 121. While certain mutations are widely present, pointing to the magnitude of the polymorphisms at these loci, others are not common, suggesting diversity in the multidrug-resistant M. tuberculosis strains prevalent in this region. Our results additionally have implications for the development of methods for multidrug resistance detection and are also relevant in the shaping of future clinical treatment regimens and drug design strategies.

scholarly journals Second-line anti-tuberculosis drug resistance and its genetic determinants in multidrug-resistant Mycobacterium tuberculosis clinical isolates

2016 ◽  
Vol 49 (3) ◽  
pp. 439-444 ◽  
Author(s):  
Zofia Bakuła ◽  
Agnieszka Napiórkowska ◽  
Michał Kamiński ◽  
Ewa Augustynowicz-Kopeć ◽  
Zofia Zwolska ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Mycobacterium Tuberculosis ◽  
Multidrug Resistant ◽  
Clinical Isolates ◽  
Second Line ◽  
Genetic Determinants

scholarly journals Resazurin Microtiter Assay Plate: Simple and Inexpensive Method for Detection of Drug Resistance in Mycobacterium tuberculosis

2002 ◽  
Vol 46 (8) ◽  
pp. 2720-2722 ◽  
Author(s):  
Juan-Carlos Palomino ◽  
Anandi Martin ◽  
Mirtha Camacho ◽  
Humberto Guerra ◽  
Jean Swings ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Mycobacterium Tuberculosis ◽  
Multidrug Resistant ◽  
Clinical Isolates ◽  
Inexpensive Method ◽  
Antituberculosis Drugs ◽  
Specificity And Sensitivity ◽  
Proportion Method ◽  
Microtiter Assay

ABSTRACT A method for detecting multidrug-resistant Mycobacterium tuberculosis by using a reduction of resazurin is described. Eighty clinical isolates were evaluated against isoniazid and rifampin; results at 7 days were compared with those of the proportion method. Specificity and sensitivity were excellent. The method is simple, inexpensive, and rapid and might be used with other antituberculosis drugs.

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