Farzaneh ShimaSadat, Norouzi Fatemeh, Fazeli Hossein, Salehi Mahshid, Safari Marzieh, Nasr Esfahani Bahram
Department of Microbiology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran.
Department of Microbiology, School of Medicine, Fasa University of Medical Sciences, Fasa, Iran.
J Infect Dev Ctries. 2024 Feb 29;18(2):243-250. doi: 10.3855/jidc.18634.
Tuberculosis (TB) remains a serious public health problem worldwide. Drug-resistant TB is considered a major and growing global threat. Despite the great variety of described mutations in Mycobacterium tuberculosis (MTB) resistance genes, the mechanisms of drug resistance are still controversial. Recently, a report on the role of efflux pump genes in drug resistance added to this complexity. Therefore, a thorough understanding of efflux pump genes in drug-resistant TB clinical isolates is needed.
We performed molecular analysis of the efflux pump gene (Rv1258c) in 33 drug-resistant and 20 drug-sensitive clinical MTB isolates by sequencing the amplicons' targets in both the forward and reverse directions.
A novel mutation of the Rv1258c gene was identified at G442A (Ala148Thr) in rifampicin mono-resistant clinical strain, as compared to the H37Rv reference strain. In addition, a cytosine nucleotide insertion was found between the positions 580 and 581 (denominated Tap580) in two drug-sensitive strains at identical gene positions.
These results indicated the possibility of mutation in the efflux pump genes and the important role of Tap efflux pump genes in drug-resistant MTB isolates. However, further research is required to determine the direct association of these mutations with resistant MTB.
结核病在全球范围内仍然是一个严重的公共卫生问题。耐多药结核病被认为是一个日益严重的重大全球威胁。尽管在结核分枝杆菌（MTB）耐药基因中描述了各种各样的突变，但耐药机制仍存在争议。最近，一份关于外排泵基因在耐药性中作用的报告增加了这种复杂性。因此，需要深入了解耐多药结核病临床分离株中的外排泵基因。
我们通过对扩增子靶标进行正向和反向测序，对33株耐多药和20株敏感的临床MTB分离株中的外排泵基因（Rv1258c）进行了分子分析。
与H37Rv参考菌株相比，在利福平单耐药临床菌株中，Rv1258c基因在G442A（Ala148Thr）处发现了一个新的突变。此外，在两个敏感菌株的相同基因位置，580和581位之间发现了一个胞嘧啶核苷酸插入（命名为Tap580）。
这些结果表明外排泵基因存在突变的可能性，以及Tap外排泵基因在耐多药MTB分离株中的重要作用。然而，需要进一步研究来确定这些突变与耐多药MTB的直接关联。
