Unequal distribution of resistance-conferring mutations among Mycobacterium tuberculosis and Mycobacterium africanum strains from Ghana
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2010-11
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Abstract
Isoniazid (INH) and rifampicin (RMP) resistance in Mycobacterium tuberculosis complex (MTC) isolates are mainly based on mutations in a limited number of genes. However, mutation frequencies vary in different mycobacterial populations. In this work, we analyzed the distribution of resistance-associated mutations in M. tuberculosis and M. africanum strains from Ghana, West Africa. The distribution of mutations in katG, fabG1-inhA, ahpC, and rpoB was determined by DNA sequencing in 217 INH-resistant (INH r) and 45 multidrug-resistant (MDR) MTC strains isolated in Ghana from 2001 to 2004. A total of 247 out of 262 strains investigated (94.3%) carried a mutation in katG (72.5%), fabG1-inhA (25.1%), or ahpC (6.5%), respectively. M. tuberculosis strains mainly had katG 315 mutations (80.1%), whereas this proportion was significantly lower in M. africanum West-African 1 (WA1) strains (43.1%; p<0.05). In contrast, WA1 strains showed more mutations in the fabG1-inhA region (39.2%, p<0.05) compared to M. tuberculosis strains (20.9%). In 44 of 45 MDR strains (97.8%) mutations in the 81-bp core region of the rpoB gene could be verified. Additionally, DNA sequencing revealed that 5 RMP-susceptible strains also showed mutations in the rpoB hotspot region. In conclusion, although principally the same genes were affected in INH r M. tuberculosis and M. africanum strains, disequilibrium in the distribution of mutations conferring resistance was verified that might influence the efficiency of molecular tests for determination of resistance.
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EMTREE drug terms: ahpC protein; bacterial protein; fabg1 inha protein; isoniazid; KatG protein; rifampicin; RNA polymerase beta subunit; unclassified drug, EMTREE medical terms: antibiotic resistance; article; bacterial strain; bacterium isolate; controlled study; DNA sequence; gene mutation; Ghana; human; multidrug resistance; mutational analysis; Mycobacterium africanum; Mycobacterium tuberculosis; nonhuman, MeSH: Antitubercular Agents; Bacterial Proteins; DNA, Bacterial; Drug Resistance, Bacterial; Ghana; Humans; Isoniazid; Mutation; Mycobacterium; Rifampin; Sequence Analysis, DNA; Tuberculosis
Citation
Homolka, S., Meyer, C. G., Hillemann, D., Owusu-Dabo, E., Adjei, O., Horstmann, R. D., ... & Niemann, S. (2010). Unequal distribution of resistance-conferring mutations among< i> Mycobacterium tuberculosis</i> and< i> Mycobacterium africanum</i> strains from Ghana. International Journal of Medical Microbiology, 300(7), 489-495.