Autor: |
Sandhya Shekar, Zhen Xuan Yeo, Joshua C L Wong, Maurice K L Chan, Danny C T Ong, Pumipat Tongyoo, Sin-Yew Wong, Ann S G Lee |
Jazyk: |
angličtina |
Rok vydání: |
2014 |
Předmět: |
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Zdroj: |
PLoS ONE, Vol 9, Iss 7, p e102383 (2014) |
Druh dokumentu: |
article |
ISSN: |
1932-6203 |
DOI: |
10.1371/journal.pone.0102383 |
Popis: |
Isoniazid (INH) is a highly effective antibiotic central for the treatment of Mycobacterium tuberculosis (MTB). INH-resistant MTB clinical isolates are frequently mutated in the katG gene and the inhA promoter region, but 10 to 37% of INH-resistant clinical isolates have no detectable alterations in currently known gene targets associated with INH-resistance. We aimed to identify novel genes associated with INH-resistance in these latter isolates.INH-resistant clinical isolates of MTB were pre-screened for mutations in the katG, inhA, kasA and ndh genes and the regulatory regions of inhA and ahpC. Twelve INH-resistant isolates with no mutations, and 17 INH-susceptible MTB isolates were subjected to whole genome sequencing. Phylogenetically related variants and synonymous mutations were excluded and further analysis revealed mutations in 60 genes and 4 intergenic regions associated with INH-resistance. Sanger sequencing verification of 45 genes confirmed that mutations in 40 genes were observed only in INH-resistant isolates and not in INH-susceptible isolates. The ratios of non-synonymous to synonymous mutations (dN/dS ratio) for the INH-resistance associated mutations identified in this study were 1.234 for INH-resistant and 0.654 for INH-susceptible isolates, strongly suggesting that these mutations are indeed associated with INH-resistance.The discovery of novel targets associated with INH-resistance described in this study may potentially be important for the development of improved molecular detection strategies. |
Databáze: |
Directory of Open Access Journals |
Externí odkaz: |
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