Sorbonne Université, INSERM, U1135, Centre d'Immunologie et des Maladies Infectieuses, Cimi-Paris, Paris, France.
Sorbonne Université, INSERM, U1135, Centre d'Immunologie et des Maladies Infectieuses, Cimi-Paris, Paris, France; AP-HP, Sorbonne-Université, Hôpital Pitié-Salpêtrière, Centre National de Référence des Mycobactéries et de la Résistance des Mycobactéries aux Antituberculeux, Paris, France.
Clin Microbiol Infect. 2021 Nov;27(11):1601-1612. doi: 10.1016/j.cmi.2021.07.007. Epub 2021 Jul 13.
The fact that Mycobacterium leprae does not grow in vitro remains a challenge in the survey of its antimicrobial resistance (AMR). Mainly molecular methods are used to diagnose AMR in M. leprae to provide reliable data concerning mutations and their impact. Fluoroquinolones (FQs) are efficient for the treatment of leprosy and the main second-line drugs in case of multidrug resistance.
This study aimed at performing a systematic review (a) to characterize all DNA gyrase gene mutations described in clinical isolates of M. leprae, (b) to distinguish between those associated with FQ resistance or susceptibility and (c) to delineate a consensus numbering system for M. leprae GyrA and GyrB.
Data source was PubMed.
Publications reporting genotypic susceptibility-testing methods and gyrase gene mutations in M. leprae clinical strains.
In 25 studies meeting our inclusion criteria, 2884 M. leprae isolates were analysed (2236 for gyrA only (77%) and 755 for both gyrA and gyrB (26%)): 3.8% of isolates had gyrA mutations (n = 110), mostly at position 91 (n = 75, 68%) and 0.8% gyrB mutations (n = 6). Since we found discrepancies regarding the location of substitutions associated with FQ resistance, we established a consensus numbering system to properly number the mutations. We also designed a 3D model of the M. leprae DNA gyrase to predict the impact of mutations whose role in FQ-susceptibility has not been demonstrated previously.
Mutations in DNA gyrase are observed in 4% of the M. leprae clinical isolates. To solve discrepancies among publications and to distinguish between mutations associated with FQ resistance or susceptibility, the consensus numbering system we proposed as well as the 3D model of the M. leprae gyrase for the evaluation of the impact of unknown mutations in FQ resistance, will provide help for resistance surveillance.
麻风分枝杆菌无法在体外生长，这给其抗微生物药物耐药性（AMR）调查带来了挑战。目前主要采用分子方法来诊断麻风分枝杆菌的 AMR，以提供有关突变及其影响的可靠数据。氟喹诺酮类（FQs）是治疗麻风病的有效药物，也是多药耐药情况下的主要二线药物。
本研究旨在进行系统评价：（a）描述临床分离的麻风分枝杆菌中所有 DNA 回旋酶基因突变特征；（b）区分与 FQ 耐药或敏感相关的突变；（c）为麻风分枝杆菌 GyrA 和 GyrB 制定共识编号系统。
数据来源为 PubMed。
报道了麻风分枝杆菌临床株基因药敏检测方法和回旋酶基因突变的出版物。
在符合纳入标准的 25 项研究中，共分析了 2884 株麻风分枝杆菌分离株（仅 2236 株进行了 gyrA 分析（77%），755 株进行了 gyrA 和 gyrB 分析（26%））：3.8%的分离株存在 gyrA 突变（n=110），主要位于位置 91（n=75，68%）和 0.8% gyrB 突变（n=6）。由于我们发现与 FQ 耐药相关的替代位置存在差异，因此我们建立了一个共识编号系统，以正确编号突变。我们还设计了麻风分枝杆菌 DNA 回旋酶的 3D 模型，以预测先前未证明与 FQ 敏感性相关的突变的影响。
在 4%的麻风分枝杆菌临床分离株中观察到 DNA 回旋酶突变。为了解决文献中的差异，并区分与 FQ 耐药或敏感相关的突变，我们提出的共识编号系统以及麻风分枝杆菌回旋酶的 3D 模型，用于评估未知 FQ 耐药性突变的影响，将为耐药监测提供帮助。
