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首页> 外文期刊>Journal of genetics >Fitness-compensatory mutations facilitate the spread of drug-resistant F15/LAM4/KZN and F28 Mycobacterium tuberculosis strains in KwaZulu-Natal, South Africa
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Fitness-compensatory mutations facilitate the spread of drug-resistant F15/LAM4/KZN and F28 Mycobacterium tuberculosis strains in KwaZulu-Natal, South Africa

机译：健身 - 补偿突变促进毒品抗药性F15 / LAM4 / KZN和F28分枝杆菌结核病菌株在南非南非

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While the acquisition of drug resistance is often accompanied by fitness costs, Mycobacterium tuberculosis has developed mechanisms to overcome these costs in the form of compensatory mutations. In an attempt to dissect strain-specific differences in biological fitness, 10 M. tuberculosis genomes, representing F15/LAM4/KZN, Beijing, F11 and F28 genotypes were sequenced on the Illumina MiSeq platform. Drug-susceptible F15/LAM4/KZN strains differed by 43 SNPs, demonstrating that heterogeneity exists even among closely-related strains. We found unique, nonsynonymous single-nucleotide polymorphisms (SNPs) in the sigA and grcC1 genes of multidrug resistant (MDR) and XDR F15/LAM4/KZN strains, respectively. The F28 MDR strain harboured a novel ubiA mutation in combination with its embB M306I mutation, which may be related to ethambutol resistance. In addition, it possessed a low-frequency rpoC mutation, suggesting that this strain was in the process of developing compensation. In contrast, no compensatory mutations were identified in Beijing and F11 MDR strains, corroborating its low in vitro fitness. Clinical strains also harboured unique SNPs in a number of important genes associated with virulence, highlighting the need for future studies which examine the correlation of genetic variations with phenotypic diversity. In summary, whole-genome sequencing revealed the presence of fitness-compensatory mutations in F15/LAM4/KZN and F28 genotypes which predominate in MDR and/or extensively drug resistant (XDR) forms in KwaZulu-Natal, South Africa.
机译：虽然收购耐药性往往伴有健身成本，但结核分枝杆菌产生了克服这些成本以补偿性突变的形式产生的机制。在Illumina Miseq平台上测序了在Illumina MiSeq平台上测序了10米结核病基因组，代表F15 / LAM4 / KZN，北京，F11和F28基因型的菌株的特异性差异。药物易感的F15 / LAM4 / KZN菌株差异为43个SNP，表明即使在与密切相关的菌株中也存在异质性。我们在多药物（MDR）和XDR F15 / Lam4 / KZN菌株的SIGA和GCC1基因中发现了独特的非型单核苷酸多态性（SNP）。 F28 MDR菌株与其栓塞M306I突变结合突出了一种新的UBIa突变，这可能与乙胺醇抗性有关。此外，它具有低频的RPOC突变，表明这种菌株是在开发补偿的过程中。相比之下，在北京和F11 MDR菌株中没有鉴定补偿性突变，证实其低体外适应性。临床菌株也在与毒力相关的许多重要基因中患有独特的SNP，突出了对未来研究的需求，这些研究检查了遗传变异与表型多样性的相关性。总之，全基因组测序揭示了F15 / LAM4 / KZN和F28基因型中健身补偿性突变的存在，其在南非夸祖鲁 - 纳塔尔岛的MDR和/或广泛的毒性（XDR）形式中占有平。

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