Prevalence and patterns of rifampicin and isoniazid resistance conferring mutations in Mycobacterium tuberculosis isolates from Uganda.
Prevalence and patterns of rifampicin and isoniazid resistance conferring mutations in Mycobacterium tuberculosis isolates from Uganda.
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DOI：
10.1371/journal.pone.0198091
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发表时间：
2018
期刊：
影响因子：
3.7
通讯作者：
Kateete DP
中科院分区：
文献类型：
--
作者：
Kigozi E;Kasule GW;Musisi K;Lukoye D;Kyobe S;Katabazi FA;Wampande EM;Joloba ML;Kateete DP
结核病的准确诊断，特别是通过使用快速分子检测，可以减少耐药结核病在社区中的传播。然而，赋予耐药性的突变频率随结核分枝杆菌的地理位置而变化，这影响了快速分子检测检测耐药性的效率。这就产生了对来自不同环境的耐药分离株进行表征的需要，以研究赋予耐药性的突变的频率。在这里，我们描述了乌干达分离株中利福平和异烟肼耐药突变的流行率和模式，这可能有助于管理乌干达和撒哈拉以南非洲其他国家的耐多药结核病患者。对 97 株结核分枝杆菌分离株进行了鉴定，其中 38 株具有多重耐药性，7 株对利福平耐药，12 株对异烟肼单药耐药，40 株对利福平和异烟肼敏感。 rpoB 利福平耐药决定区 (rpoB/RRDR) 的序列分析显示 6 个密码子存在突变：588、531、526、516、513 和 511，其中 Ser531Leu 最常见（40%，18/45）。总体而言，经常与利福平耐药相关的三种突变（Ser531Leu、His526Tyr、Asp516Tyr）发生在 76% 的利福平耐药菌株中，而 18% (8/45) 的利福平耐药菌株缺乏 rpoB/RRDR 突变。此外，katG和inhA基因启动子的序列分析分别主要揭示了Ser315Thr（76％，38/50）和C（-15）T（8％，4/50）突变。这两种突变通常与异烟肼耐药相关，发生在 88% 的异烟肼耐药菌株中。然而，20% (10/50) 的异烟肼耐药菌株缺乏 katG 和 inhA 基因启动子突变。 rpoB/RRDR 通过检测高置信度突变（Ser531Leu、His526Tyr、Asp516Tyr）序列分析对利福平耐药的敏感性为 81%，而通过检测高置信度突变（Ser315Thr、C(-15)T、 T(-8)C)。此外，考虑到乌干达的循环结核病基因型，异烟肼耐药突变在乌干达结核分枝杆菌谱系4/亚谱系中更为频繁，这或许可以解释为什么该基因型与耐多药结核病的相关性较弱。 rpoB/RRDR、katG 和 inhA 基因启动子的序列分析可用于检测乌干达对利福平/异烟肼耐药的结核分枝杆菌分离株，但约 ≤20% 的耐药分离株缺乏已知的赋予耐药性的突变，因此快速分子测定可能无法检测到它们具有耐药性。
Accurate diagnosis of tuberculosis, especially by using rapid molecular assays, can reduce transmission of drug resistant tuberculosis in communities. However, the frequency of resistance conferring mutations varies with geographic location of Mycobacterium tuberculosis, and this affects the efficiency of rapid molecular assays in detecting resistance. This has created need for characterizing drug resistant isolates from different settings to investigate frequencies of resistance conferring mutations. Here, we describe the prevalence and patterns of rifampicin- and isoniazid- resistance conferring mutations in isolates from Uganda, which could be useful in the management of MDR-TB patients in Uganda and other countries in sub-Saharan Africa. Ninety seven M. tuberculosis isolates were characterized, of which 38 were MDR, seven rifampicin-resistant, 12 isoniazid-mono-resistant, and 40 susceptible to rifampicin and isoniazid. Sequence analysis of the rpoB rifampicin-resistance determining region (rpoB/RRDR) revealed mutations in six codons: 588, 531, 526, 516, 513, and 511, of which Ser531Leu was the most frequent (40%, 18/45). Overall, the three mutations (Ser531Leu, His526Tyr, Asp516Tyr) frequently associated with rifampicin-resistance occurred in 76% of the rifampicin resistant isolates while 18% (8/45) of the rifampicin-resistant isolates lacked mutations in rpoB/RRDR. Furthermore, sequence analysis of katG and inhA gene promoter revealed mainly the Ser315Thr (76%, 38/50) and C(-15)T (8%, 4/50) mutations, respectively. These two mutations combined, which are frequently associated with isoniazid-resistance, occurred in 88% of the isoniazid resistant isolates. However, 20% (10/50) of the isoniazid-resistant isolates lacked mutations both in katG and inhA gene promoter. The sensitivity of sequence analysis of rpoB/RRDR for rifampicin-resistance via detection of high confidence mutations (Ser531Leu, His526Tyr, Asp516Tyr) was 81%, while it was 77% for analysis of katG and inhA gene promoter to detect isoniazid-resistance via detection of high confidence mutations (Ser315Thr, C(-15)T, T(-8)C). Furthermore, considering the circulating TB genotypes in Uganda, the isoniazid-resistance conferring mutations were more frequent in M. tuberculosis lineage 4/sub-lineage Uganda, perhaps explaining why this genotype is weakly associated with MDR-TB. Sequence analysis of rpoB/RRDR, katG and inhA gene promoter is useful in detecting rifampicin/isoniazid resistant M. tuberculosis isolates in Uganda however, about ≤20% of the resistant isolates lack known resistance-conferring mutations hence rapid molecular assays may not detect them as resistant.
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影响因子：
3.7
作者：
Lukoye D;Cobelens FG;Ezati N;Kirimunda S;Adatu FE;Lule JK;Nuwaha F;Joloba ML
通讯作者：
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影响因子：
3.7
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3.7
作者：
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通讯作者：
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影响因子：
9.4
作者：
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