Association between embB Codon 306 Mutations, Phenotypic Resistance Profiles, and Genotypic Characterization in Clinical Mycobacterium tuberculosis Isolates from Hebei, China
| Autor: | Yu-Ling Wang, Shumin Zhang, Jian-Hua Lu, Zun‐gui Xu, Erhei Dai, Zhi Zhang, Jin-Feng Cao, Yu-Zhen Liu, Hai-Bin Wang, Yanan Li, Huixia Gao |
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| Rok vydání: | 2016 |
| Předmět: |
DNA
Bacterial 0301 basic medicine China Tuberculosis 030106 microbiology Antitubercular Agents Locus (genetics) Microbial Sensitivity Tests Drug resistance Mycobacterium tuberculosis 03 medical and health sciences Mechanisms of Resistance Drug Resistance Multiple Bacterial Tuberculosis Multidrug-Resistant Genotype Isoniazid medicine Humans Pharmacology (medical) Pentosyltransferases Tuberculosis Pulmonary Ethambutol Pharmacology Genetics Base Sequence biology Sequence Analysis DNA medicine.disease biology.organism_classification Multiple drug resistance Infectious Diseases Rifampin medicine.drug |
| Zdroj: | Antimicrobial Agents and Chemotherapy. 60:7295-7302 |
| ISSN: | 1098-6596 0066-4804 |
| Popis: | Ethambutol (EMB) is an essential first-line drug for tuberculosis (TB) treatment. Nucleotide substitutions at embB codon 306 ( embB 306) have been proposed to be a potential marker for EMB resistance and a predictor of broad drug resistance in clinical Mycobacterium tuberculosis isolates. However, discordant findings about the association between embB 306 mutations and EMB resistance were reported. Hebei Province is located in the Beijing-Tianjin-Hebei integration region in China; however, little information about the genetic diversity of the embB locus in this area is available. In this study, we sequenced the region surrounding embB 306 (codons 207 to 445) in 62 ethambutol-resistant (EMB r ) isolates, 214 ethambutol-susceptible isolates resistant to other first-line drugs (EMB s isolates), and 100 pan-sensitive isolates. Our data indicated that none of the pan-sensitive isolates showed mutations at embB 306 and 63 drug-resistant isolates harbored embB 306 substitutions, with these substitutions being found in 56.5% (35/62) of EMB r isolates and 13.1% (28/214) of EMB s isolates. A significant association between the embB 306 mutation and resistance to isoniazid, rifampin, EMB, and multiple drugs was observed, and the rate of mutation of embB 306 increased with increasing numbers of first-line drugs to which the isolates were resistant. The embB 306 mutation is not the sole causative factor for EMB resistance, and the poor sensitivity limits its utility as a marker for drug-resistant TB. However, it may be a potential marker for broad drug resistance, especially for multidrug resistance. The mycobacterial interspersed repetitive unit–variable-number tandem-repeat profiles may serve as markers for predicting the embB 306 substitutions that may occur in drug-resistant M. tuberculosis isolates under antimicrobial selection pressure. |
| Databáze: | OpenAIRE |
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