Unequal distribution of resistance-conferring mutations among Mycobacterium tuberculosis and Mycobacterium africanum strains from Ghana
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2010
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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 (INHr
) 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 INHr 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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This article is published by Elsevier and is also available at www.elsevier.de/ijmm
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International Journal of Medical Microbiology 300 (2010) 489–495