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https://hdl.handle.net/1822/26987
Título: | Systematic review of allelic exchange experiments aimed at identifying mutations that confer drug resistance in Mycobacterium tuberculosis |
Autor(es): | Guimarães, Hanna Nebenzahl Jacobson, Karen R. Farhat, Maha R. Murray, Megan B. |
Palavras-chave: | M. tuberculosis Microbial susceptibility tests Genetics SNPs in vitro resistance M tuberculosis |
Data: | 2014 |
Editora: | Oxford University Press |
Revista: | Journal of antimicrobial chemotherapy |
Resumo(s): | BACKGROUND: Improving our understanding of the relationship between the genotype and the drug resistance phenotype of Mycobacterium tuberculosis will aid the development of more accurate molecular diagnostics for drug-resistant tuberculosis. Studies that use direct genetic manipulation to identify the mutations that cause M. tuberculosis drug resistance are superior to associational studies in elucidating an individual mutation's contribution to the drug resistance phenotype. METHODS: We systematically reviewed the literature for publications reporting allelic exchange experiments in any of the resistance-associated M. tuberculosis genes. We included studies that introduced single point mutations using specialized linkage transduction or site-directed/in vitro mutagenesis and documented a change in the resistance phenotype. RESULTS: We summarize evidence supporting the causal relationship of 54 different mutations in eight genes (katG, inhA, kasA, embB, embC, rpoB, gyrA and gyrB) and one intergenic region (furA-katG) with resistance to isoniazid, the rifamycins, ethambutol and fluoroquinolones. We observed a significant role for the strain genomic background in modulating the resistance phenotype of 21 of these mutations and found examples of where the same drug resistance mutations caused varying levels of resistance to different members of the same drug class. CONCLUSIONS: This systematic review highlights those mutations that have been shown to causally change phenotypic resistance in M. tuberculosis and brings attention to a notable lack of allelic exchange data for several of the genes known to be associated with drug resistance. |
Tipo: | Artigo |
Descrição: | First published online: September 20, 2013 |
URI: | https://hdl.handle.net/1822/26987 |
DOI: | 10.1093/jac/dkt358 |
ISSN: | 0305-7453 |
Versão da editora: | http://jac.oxfordjournals.org/content/early/2013/09/19/jac.dkt358.abstract |
Arbitragem científica: | yes |
Acesso: | Acesso aberto |
Aparece nas coleções: | ICVS - Artigos em revistas internacionais / Papers in international journals |
Ficheiros deste registo:
Ficheiro | Descrição | Tamanho | Formato | |
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nebenzahl-guimaraes h_j antimicrob chemother 2013 posp.pdf | 288,1 kB | Adobe PDF | Ver/Abrir |