Zofia Bakuła1, Agnieszka Napiórkowska2, Michał Kamiński1, Ewa Augustynowicz-Kopeć2, Zofia Zwolska2, Jacek Bielecki1, Tomasz Jagielski3. 1. Department of Applied Microbiology, Institute of Microbiology, Faculty of Biology, University of Warsaw, 02-096 Warsaw, Poland. 2. Department of Microbiology, National Tuberculosis and Lung Diseases Research Institute, 01-138 Warsaw, Poland. 3. Department of Applied Microbiology, Institute of Microbiology, Faculty of Biology, University of Warsaw, 02-096 Warsaw, Poland. Electronic address: t.jagielski@biol.uw.edu.pl.
Abstract
BACKGROUND: Mutations in several genetic loci have been implicated in the development of resistance to second-line anti-tuberculosis (TB) drugs (SLDs). The purpose of this study was to investigate the prevalence of resistance to SLDs and its association with specific mutations in multidrug-resistant (MDR) Mycobacterium tuberculosis clinical isolates. MATERIALS AND METHODS: The study included 46 MDR-TB isolates. Mutation profiling was performed by amplifying and sequencing the following six genes: gyrA/gyrB, rrs, tlyA, and ethA/ethR, in which mutations are implicated in resistance of tubercle bacilli to ofloxacin (OFX), amikacin (AMK), capreomycin, and ethionamide (ETH), respectively. RESULTS: Of the strains analyzed, 14 (30.4%) showed resistance to at least one of the four SLDs tested. Mutations in the gyrA gene occurred in 34 (73.9%) strains, with the most common amino acid change being Ser95Thr. The Asp94Asn and Ala90Val substitutions in the gyrA were present exclusively in OFX-resistant strains, yet represented only 40% of all OFX-resistant strains. The only mutation in the gyrB gene was substitution Ser447Phe, detected in one OFX-resistant isolate. None of the AMK-resistant strains carried a mutation in the rrs gene. Mutations in the ethA/ethR loci were found in one ETH-resistant and 11 ETH-susceptible strains. CONCLUSIONS: The results of this study challenge the usefulness of sequence analyses of tested genes (except gyrA) for the prediction of SLD resistance patterns and highlight the need for searching other genetic loci for detection of mutations conferring resistance to SLDs in M. tuberculosis.
BACKGROUND: Mutations in several genetic loci have been implicated in the development of resistance to second-line anti-tuberculosis (TB) drugs (SLDs). The purpose of this study was to investigate the prevalence of resistance to SLDs and its association with specific mutations in multidrug-resistant (MDR) Mycobacterium tuberculosis clinical isolates. MATERIALS AND METHODS: The study included 46 MDR-TB isolates. Mutation profiling was performed by amplifying and sequencing the following six genes: gyrA/gyrB, rrs, tlyA, and ethA/ethR, in which mutations are implicated in resistance of tubercle bacilli to ofloxacin (OFX), amikacin (AMK), capreomycin, and ethionamide (ETH), respectively. RESULTS: Of the strains analyzed, 14 (30.4%) showed resistance to at least one of the four SLDs tested. Mutations in the gyrA gene occurred in 34 (73.9%) strains, with the most common amino acid change being Ser95Thr. The Asp94Asn and Ala90Val substitutions in the gyrA were present exclusively in OFX-resistant strains, yet represented only 40% of all OFX-resistant strains. The only mutation in the gyrB gene was substitution Ser447Phe, detected in one OFX-resistant isolate. None of the AMK-resistant strains carried a mutation in the rrs gene. Mutations in the ethA/ethR loci were found in one ETH-resistant and 11 ETH-susceptible strains. CONCLUSIONS: The results of this study challenge the usefulness of sequence analyses of tested genes (except gyrA) for the prediction of SLD resistance patterns and highlight the need for searching other genetic loci for detection of mutations conferring resistance to SLDs in M. tuberculosis.
Authors: Y Hu; L Xu; Y L He; Y Pang; N Lu; J Liu; J Shen; D M Zhu; X Feng; Y W Wang; C Yang Journal: Biomed Res Int Date: 2017-07-17 Impact factor: 3.411
Authors: Eunjin Cho; Su Jin Lee; Jiyoung Lim; Dong Sik Kim; Namil Kim; Han Oh Park; Ji-Im Lee; Eunsoon Son; Sang Nae Cho; Wah Wah Aung; Jong Seok Lee Journal: J Clin Tuberc Other Mycobact Dis Date: 2022-02-09