Characterization of mutations in multi- and extensive drug resistance among strains of Mycobacterium tuberculosis clinical isolates in Republic of Korea

2013 ◽  
Vol 76 (2) ◽  
pp. 187-196 ◽  
Author(s):  
Hum Nath Jnawali ◽  
Sung Chul Hwang ◽  
Young Kil Park ◽  
Hyejin Kim ◽  
Yeong Seon Lee ◽  
...  
2010 ◽  
Vol 54 (11) ◽  
pp. 4789-4793 ◽  
Author(s):  
Alka Khanna ◽  
V. Samuel Raj ◽  
Bansidhar Tarai ◽  
Ruchi Sood ◽  
Pawan Kumar Pareek ◽  
...  

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.


2019 ◽  
Vol 8 (4) ◽  
pp. 320
Author(s):  
MohdSalleh Zaki ◽  
MohdNur Noorizhab Fakhruzzaman ◽  
NorzulianaZainal Abidin ◽  
ZirwatulAdilah Aziz ◽  
WaiFeng Lim ◽  
...  

2011 ◽  
Vol 55 (12) ◽  
pp. 5654-5659 ◽  
Author(s):  
Asho Ali ◽  
Rumina Hasan ◽  
Kauser Jabeen ◽  
Nusrat Jabeen ◽  
Ejaz Qadeer ◽  
...  

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.


2014 ◽  
Vol 59 (1) ◽  
pp. 414-420 ◽  
Author(s):  
Kanchan Ajbani ◽  
Shou-Yean Grace Lin ◽  
Camilla Rodrigues ◽  
Duylinh Nguyen ◽  
Francine Arroyo ◽  
...  

ABSTRACTReliable molecular diagnostics, which detect specific mutations associated with drug resistance, are promising technologies for the rapid identification and monitoring of drug resistance inMycobacterium tuberculosisisolates. Pyrosequencing (PSQ) has the ability to detect mutations associated with first- and second-line anti-tuberculosis (TB) drugs, with the additional advantage of being rapidly adaptable for the identification of new mutations. The aim of this project was to evaluate the performance of PSQ in predicting phenotypic drug resistance in multidrug- and extensively drug-resistant tuberculosis (M/XDR-TB) clinical isolates from India, South Africa, Moldova, and the Philippines. A total of 187 archived isolates were run through a PSQ assay in order to identifyM. tuberculosis(via the IS6110marker), and to detect mutations associated with M/XDR-TB within small stretches of nucleotides in selected loci. The molecular targets includedkatG, theinhApromoter and theahpC-oxyRintergenic region for isoniazid (INH) resistance; therpoBcore region for rifampin (RIF) resistance;gyrAfor fluoroquinolone (FQ) resistance; andrrsfor amikacin (AMK), capreomycin (CAP), and kanamycin (KAN) resistance. PSQ data were compared to phenotypic mycobacterial growth indicator tube (MGIT) 960 drug susceptibility testing results for performance analysis. The PSQ assay illustrated good sensitivity for the detection of resistance to INH (94%), RIF (96%), FQ (93%), AMK (84%), CAP (88%), and KAN (68%). The specificities of the assay were 96% for INH, 100% for RIF, FQ, AMK, and KAN, and 97% for CAP. PSQ is a highly efficient diagnostic tool that reveals specific nucleotide changes associated with resistance to the first- and second-line anti-TB drug medications. This methodology has the potential to be linked to mutation-specific clinical interpretation algorithms for rapid treatment decisions.


2014 ◽  
Vol 48 (2) ◽  
pp. 214-226 ◽  
Author(s):  
D. V. Zimenkov ◽  
E. V. Kulagina ◽  
O. V. Antonova ◽  
S. A. Surzhikov ◽  
Yu. A. Bespyatykh ◽  
...  

2010 ◽  
Vol 65 (11) ◽  
pp. 2341-2346 ◽  
Author(s):  
G. Tudo ◽  
E. Rey ◽  
S. Borrell ◽  
F. Alcaide ◽  
G. Codina ◽  
...  

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