Whole genome sequencing based characterization of extensively drug-resistant Mycobacterium tuberculosis isolates from Pakistan.
Whole genome sequencing based characterization of extensively drug-resistant Mycobacterium tuberculosis isolates from Pakistan.
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DOI：
10.1371/journal.pone.0117771
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Hasan R
中科院分区：
文献类型：
--
作者：
Ali A;Hasan Z;McNerney R;Mallard K;Hill-Cawthorne G;Coll F;Nair M;Pain A;Clark TG;Hasan R
需要改进检测结核分枝杆菌（MTB）菌株耐药性的分子诊断方法。对一线和二线抗结核药物的耐药性与特定基因的单核苷酸多态性（SNP）有关。然而，这些SNP在MTB谱系之间可能不同，因此需要当地数据来描述不同的菌株群体。我们使用全基因组测序（WGS）来表征来自巴基斯坦的37株广泛耐药（XDR）MTB分离株，并研究了40个与耐药性相关的基因。利福平耐药归因于rpoB热点区域的SNP。异烟肼耐药最常见的与katG密码子315（92%）突变相关，其次是inhA S94 A（8%），然而，一种菌株在katG，inhA或oxyR-ahpC中没有SNP。所有菌株均对吡嗪酰胺耐药，但只有43%具有pncA SNP。乙胺丁醇耐药菌株主要有embB密码子306（62%）突变，但在embB密码子406，378和328也存在额外的SNP。81%的菌株对氟喹诺酮类药物的耐药性与gyrA 91-94密码子相关; 4种菌株仅具有gyrB突变，而其他菌株在gyrA或gyrB中均没有SNP。链霉素耐药菌株在核糖体RNA基因中有突变; rpsL密码子43（42%）; rrs 500区域（16%）和gidB（34%），而6株在这些基因中没有任何突变。阿米卡星/卡那霉素/卷曲霉素耐药与rrs中nt 1401（78%）和nt 1484（3%）处的SNP相关，7种（19%）菌株除外。我们估计，如果只使用当前商业检测的常见热点区域靶标，这些XDR菌株的表型和基因型检测之间的一致性将在利福平（100%）、异烟肼（92%）、氟喹诺酮类（81%）、氨基糖苷类（78%）和乙胺丁醇（62%）之间变化;而pncA测序将在不到一半的分离株中提供基因型耐药。这项工作强调了扩大结核分枝杆菌分离株耐药性检测靶点的重要性。
Improved molecular diagnostic methods for detection drug resistance in Mycobacterium tuberculosis (MTB) strains are required. Resistance to first- and second- line anti-tuberculous drugs has been associated with single nucleotide polymorphisms (SNPs) in particular genes. However, these SNPs can vary between MTB lineages therefore local data is required to describe different strain populations. We used whole genome sequencing (WGS) to characterize 37 extensively drug-resistant (XDR) MTB isolates from Pakistan and investigated 40 genes associated with drug resistance. Rifampicin resistance was attributable to SNPs in the rpoB hot-spot region. Isoniazid resistance was most commonly associated with the katG codon 315 (92%) mutation followed by inhA S94A (8%) however, one strain did not have SNPs in katG, inhA or oxyR-ahpC. All strains were pyrazimamide resistant but only 43% had pncA SNPs. Ethambutol resistant strains predominantly had embB codon 306 (62%) mutations, but additional SNPs at embB codons 406, 378 and 328 were also present. Fluoroquinolone resistance was associated with gyrA 91–94 codons in 81% of strains; four strains had only gyrB mutations, while others did not have SNPs in either gyrA or gyrB. Streptomycin resistant strains had mutations in ribosomal RNA genes; rpsL codon 43 (42%); rrs 500 region (16%), and gidB (34%) while six strains did not have mutations in any of these genes. Amikacin/kanamycin/capreomycin resistance was associated with SNPs in rrs at nt1401 (78%) and nt1484 (3%), except in seven (19%) strains. We estimate that if only the common hot-spot region targets of current commercial assays were used, the concordance between phenotypic and genotypic testing for these XDR strains would vary between rifampicin (100%), isoniazid (92%), flouroquinolones (81%), aminoglycoside (78%) and ethambutol (62%); while pncA sequencing would provide genotypic resistance in less than half the isolates. This work highlights the importance of expanded targets for drug resistance detection in MTB isolates.
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影响因子：
30.8
作者：
Comas, Inaki;Borrell, Sonia;Roetzer, Andreas;Rose, Graham;Malla, Bijaya;Kato-Maeda, Midori;Galagan, James;Niemann, Stefan;Gagneux, Sebastien
通讯作者：
Gagneux, Sebastien
DOI：
10.1016/j.tube.2014.02.005
发表时间：
2014-05
期刊：
Tuberculosis (Edinburgh, Scotland)
影响因子：
--
作者：
Coll F;Preston M;Guerra-Assunção JA;Hill-Cawthorn G;Harris D;Perdigão J;Viveiros M;Portugal I;Drobniewski F;Gagneux S;Glynn JR;Pain A;Parkhill J;McNerney R;Martin N;Clark TG
通讯作者：
Clark TG
影响因子：
9.4
作者：
Honoré-Bouakline, S;Vincensini, JP;Herrmann, JL
通讯作者：
Herrmann, JL
影响因子：
5.2
作者：
Brandis, Gerrit;Hughes, Diarmaid
通讯作者：
Hughes, Diarmaid
DOI：
10.1093/bioinformatics/bts544
发表时间：
2012-11-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Coll F;Mallard K;Preston MD;Bentley S;Parkhill J;McNerney R;Martin N;Clark TG
通讯作者：
Clark TG