Significance of Coexisting Mutations on Determination of the Degree of Isoniazid Resistance inMycobacterium tuberculosisStrains
| Autor: | Chamila Priyangani Adikaram, Jennifer Perera, Galbokka Hewage Roshanthi Eranga Karunaratne, Sandhya Sulochana Wijesundera, Dhammika Vidanagama |
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| Rok vydání: | 2018 |
| Předmět: |
DNA
Bacterial 0301 basic medicine Microbiology (medical) 030106 microbiology Immunology Antitubercular Agents Microbial Sensitivity Tests medicine.disease_cause Microbiology law.invention Mycobacterium tuberculosis 03 medical and health sciences Bacterial Proteins law Drug Resistance Bacterial Tuberculosis Multidrug-Resistant Isoniazid medicine Humans Point Mutation Codon Promoter Regions Genetic Gene Polymerase chain reaction Sri Lanka Pharmacology Genetics Mutation biology INHA Point mutation Nucleic acid sequence Promoter Sequence Analysis DNA biochemical phenomena metabolism and nutrition bacterial infections and mycoses biology.organism_classification 030104 developmental biology Genes Bacterial |
| Zdroj: | Microbial Drug Resistance. 24:844-851 |
| ISSN: | 1931-8448 1076-6294 |
| DOI: | 10.1089/mdr.2017.0330 |
| Popis: | The emergence and spread of drug-resistant tuberculosis (TB) pose a threat to TB control in Sri Lanka. Isoniazid (INH) is a key element of the first-line anti-TB treatment regimen. Resistance to INH is mainly associated with point mutations in katG, inhA, and ahpC genes. The objective of this study was to determine mutations of these three genes in INH-resistant Mycobacterium tuberculosis (MTb) strains in Sri Lanka. Complete nucleotide sequence of the three genes was amplified by polymerase chain reaction and subjected to DNA sequencing. Point mutations in the katG gene were identified in 93% isolates, of which the majority (78.6%) were at codon 315. Mutations at codons 212 and 293 of the katG gene have not been reported previously. Novel mutations were recognized in the promoter region of the inhA gene (C deletion at -34), fabG1 gene (codon 27), and ahpC gene (codon 39). Single S315T mutation in the katG gene led to a high level of resistance, while a low level of resistance with high frequency (41%) was observed when katG codon 315 coexisted with the mutation at codon 463. Since most of the observed mutations of all three genes coexisted with the katG315 mutation, screening of katG315 mutations will be a useful marker for molecular detection of INH resistance of MTb in Sri Lanka. |
| Databáze: | OpenAIRE |
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