Akbari Aghababa AmirHossein, Nasiri Mohammad Javad, Pakzad Parviz, Mirsamadi Elnaz Sadat
Department of Microbiology, Faculty of Biological Sciences, North Tehran Branch, Islamic Azad University, Tehran, Iran.
Department of Microbiology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
New Microbes New Infect. 2024 May 26;60-61:101437. doi: 10.1016/j.nmni.2024.101437. eCollection 2024 Aug-Oct.
The surge of multidrug-resistant TB (MDR-TB) in Iran poses a significant challenge to global healthcare. The introduction of delamanid (DLM) and bedaquiline (BDQ), two potent antimycobacterial drugs, marks a crucial advance. Nevertheless, as resistance in is on the rise in Iran and resistance to these newer medications is emerging, investigations in this field are of utmost importance.
In this cross-sectional study, 38 MDR-TB strains were collected from five distinct regional TB laboratories in Iran. The clinical isolates were confirmed as using the phenotypic tests and IS6110-based PCR assay. Drug susceptibility testing (DST) for isoniazid, rifampicin, ethambutol, DLM, and BDQ was performed using WHO-approved methods. Sequencing was used to investigate genetic mutations in DLM (, ) and BDQ (, , ) genes associated with resistance.
Among the 38 collected MDR-TB isolates, 7 (18.5 %) exhibited resistance to DLM, while all remained susceptible to BDQ. Analysis of the sequencing data revealed that the gene exhibited the highest number of mutations in DLM-resistant isolates, including 18 nonsynonymous mutations and 1 indel leading to frameshift mutations. A common mutation, Gly81Ser, was present in 4 of the DLM-resistant isolates (4/7; 57.1 %). A synonymous mutation, T960C, in the gene was uniformly found in DLM-resistant samples. Notably, no significant mutations were observed in the , , or genes in any of the BDQ-susceptible isolates.
Our study underscores the emergence of DLM resistance in a subset of MDR-TB isolates in Iran, primarily associated with mutations in the gene. This emphasizes the ongoing necessity for TB drug resistance surveillance and research. While BDQ remains efficacious, the emergence of DLM resistance is a concerning development, warranting further exploration into resistance mechanisms and the formulation of effective TB control strategies.
伊朗耐多药结核病（MDR-TB）的激增给全球医疗保健带来了重大挑战。引入两种强效抗分枝杆菌药物德拉马尼（DLM）和贝达喹啉（BDQ）标志着一项关键进展。然而，由于伊朗耐多药结核病的耐药性正在上升，并且对这些新型药物的耐药性也在出现，因此该领域的研究至关重要。
在这项横断面研究中，从伊朗五个不同的地区结核病实验室收集了38株耐多药结核菌株。临床分离株通过表型试验和基于IS6110的PCR检测确认为耐多药结核菌株。使用世界卫生组织批准的方法对异烟肼、利福平、乙胺丁醇、DLM和BDQ进行药物敏感性测试（DST）。测序用于研究与耐药性相关的DLM（ ， ）和BDQ（ ， ， ）基因中的基因突变。
在收集的38株耐多药结核分离株中，7株（18.5%）对DLM耐药，而所有菌株对BDQ仍敏感。对测序数据的分析表明， 基因在耐DLM分离株中表现出最高数量的突变，包括18个非同义突变和1个导致移码突变的插入缺失。一种常见突变Gly81Ser存在于4株耐DLM分离株中（4/7；57.1%）。在耐DLM样本中均发现 基因中的一个同义突变T960C。值得注意的是，在任何对BDQ敏感的分离株中， 基因、 基因或 基因均未观察到显著突变。
我们的研究强调了伊朗一部分耐多药结核分离株中出现了对DLM的耐药性，主要与 基因的突变有关。这强调了持续进行结核病耐药性监测和研究的必要性。虽然BDQ仍然有效，但DLM耐药性的出现是一个令人担忧的发展，需要进一步探索耐药机制并制定有效的结核病控制策略。
