Genome analysis of multi- and extensively-drug-resistant tuberculosis from KwaZulu-Natal, South Africa.
Genome analysis of multi- and extensively-drug-resistant tuberculosis from KwaZulu-Natal, South Africa.
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来自南非夸祖鲁 - 纳塔尔省的多种耐药性结核病的基因组分析。
DOI：
10.1371/journal.pone.0007778
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发表时间：
2009-11-05
期刊：
影响因子：
3.7
通讯作者：
Sacchettini JC
中科院分区：
文献类型：
--
作者：
Ioerger TR;Koo S;No EG;Chen X;Larsen MH;Jacobs WR Jr;Pillay M;Sturm AW;Sacchettini JC
结核分枝杆菌的KZN菌株家族是南非夸祖鲁-纳塔尔地区特有的高毒性菌株，该地区最近爆发了广泛耐药结核病。为了研究耐药性的原因和演变，我们使用全基因组测序确定了几种临床分离株的DNA序列-一种药物敏感，一种多重耐药，九种广泛耐药。菌株之间的多态性分析与药物敏感性特征一致，因为观察到与异烟肼、利福平、卡那霉素、氧氟沙星、乙胺丁醇和吡嗪酰胺耐药相关的已知突变。然而，在多重耐药和广泛耐药菌株中，导致rpoB中利福平耐药和pncA中吡嗪酰胺耐药的突变位于不同的核苷酸位置，清楚地表明它们独立获得这些突变，并且XDR菌株不可能直接从MDR菌株进化而来（尽管它可能来自另一种类似的MDR菌株）。对来自夸祖鲁-纳塔尔其他地区的另外8个XDR菌株的测序表明，它们与第一个测序的菌株具有相同的耐药突变，包括与耐药相关的位点的相同多态性，支持这代表克隆扩增的理论。
The KZN strain family of Mycobacterium tuberculosis is a highly virulent strain endemic to the KwaZulu-Natal region of South Africa, which has recently experienced an outbreak of extensively-drug resistant tuberculosis. To investigate the causes and evolution of drug-resistance, we determined the DNA sequences of several clinical isolates - one drug-susceptible, one multi-drug resistant, and nine extensively drug-resistant - using whole-genome sequencing. Analysis of polymorphisms among the strains is consistent with the drug-susceptibility profiles, in that well-known mutations are observed that are correlated with resistance to isoniazid, rifampicin, kanamycin, ofloxacin, ethambutol, and pyrazinamide. However, the mutations responsible for rifampicin resistance in rpoB and pyrazinamide in pncA are in different nucleotide positions in the multi-drug-resistant and extensively drug-resistant strains, clearly showing that they acquired these mutations independently, and that the XDR strain could not have evolved directly from the MDR strain (though it could have arisen from another similar MDR strain). Sequencing of eight additional XDR strains from other areas of KwaZulu-Natal shows that they have identical drug resistant mutations to the first one sequenced, including the same polymorphisms at sites associated with drug resistance, supporting the theory that this represents a case of clonal expansion.
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DOI：
10.1084/jem.20041429
发表时间：
2004-12-20
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Matsunaga I;Bhatt A;Young DC;Cheng TY;Eyles SJ;Besra GS;Briken V;Porcelli SA;Costello CE;Jacobs WR Jr;Moody DB
通讯作者：
Moody DB
影响因子：
4.9
作者：
Aubry, A;Veziris, N;Fisher, LM
通讯作者：
Fisher, LM
影响因子：
4.9
作者：
Hazbon, Manzour Hernando;Brimacombe, Michael;Alland, David
通讯作者：
Alland, David
影响因子：
4.9
作者：
Morlock, GP;Metchock, B;Cooksey, RC
通讯作者：
Cooksey, RC
影响因子：
9.4
作者：
Kamerbeek, J;Schouls, L;vanEmbden, J
通讯作者：
vanEmbden, J