Correlating rrs and eis promoter mutations in clinical isolates of Mycobacterium tuberculosis with phenotypic susceptibility levels to the second-line injectables.
Correlating rrs and eis promoter mutations in clinical isolates of Mycobacterium tuberculosis with phenotypic susceptibility levels to the second-line injectables.
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DOI：
10.1016/j.ijmyco.2015.09.001
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发表时间：
2016-03
影响因子：
1.2
通讯作者：
Rodrigues C
中科院分区：
文献类型：
--
作者：
Kambli P;Ajbani K;Nikam C;Sadani M;Shetty A;Udwadia Z;Georghiou SB;Rodwell TC;Catanzaro A;Rodrigues C
将结核分枝杆菌（MTB）分离株中发现的rrs和eis启动子突变与阿米卡星（AMK）、卡那霉素（KAN）和卷曲霉素（CAP）的相应最低抑菌浓度（MIC）相关联。本研究分析了90株MTB临床分离株。通过MGIT 960测定了59株rrs和eis启动子基因区耐药相关突变分离株和31株野生型序列分离株的MIC，并通过GenoTypeMTBDRsl（版本1）测定。在对二线注射剂耐药的48株分离株中鉴定出rrs A1401 G突变。在11株对二线注射剂具有不同耐药性的分离株中发现了eis启动子突变C-14 T（n = 3）、G-10 C（n = 3）、G-10 A（n=3）和C-12 T（n=2）。31个分离株具有感兴趣的rrs和eis启动子基因区域的野生型序列，其中一个具有AMK、KAN和CAP抗性。A1401 G rrs突变株的AMK、KAN和CAP MIC分别为>40、>20和5- 15 mg/L。具有eis启动子突变的分离株的AMK、KAN和CAP MIC为0。25-1. 0，0。625-10和0。625-2. 5mg/L。本研究为基于存在与AMK、KAN和CAP耐药相关的基因突变预测二线注射剂的表型耐药水平提供了初步依据。结果表明，具有eis启动子突变的分离株对AMK、KAN和CAP的耐药水平始终低于具有rrs A1401 G突变的分离株。
To correlate rrs and eis promoter mutations, found in Mycobacterium tuberculosis (MTB) isolates,with corresponding Minimum Inhibitory Concentrations (MICs) of amikacin (AMK), kanamycin (KAN), and capreomycin (CAP). Ninety MTB clinical isolates were analyzed in this study. MICs were determined by MGIT 960 for 59 isolates with resistance-associated mutations in the rrs and eis promoter gene regions and 31 isolates with wild-type sequences, as determined by the GenoTypeMTBDRsl (version 1) assay. The rrs A1401G mutation was identified in 48 isolates resistant to the second line injectables. The eis promoter mutations C-14T (n=3), G-10C (n=3), G-10A (n=3), and C-12T (n=2) were found within 11 isolates with various resistance profiles to the second line injectables. Thirty-one isolates had wild-type sequences for the rrs and eis promoter gene regions of interest, one of which was AMK, KAN and CAP-resistant. Isolates with the A1401G rrs mutation had AMK, KAN, and CAP MICs of >40, >20, and 5–15mg/L, respectively. Isolates with eis promoter mutations had AMK, KAN, and CAP MICs of 0. 25–1. 0, 0. 625–10, and 0. 625–2. 5mg/L, respectively. This study provides a preliminary basis for the prediction of phenotypic resistance levels to the second line injectables based upon the presence of genetic mutations associated with AMK, KAN and CAP-resistance. Results suggest that isolates with eis promoter mutations have consistently lower resistance levels to AMK, KAN, and CAP than isolates with the rrs A1401G mutation.