VBIC, INSERM U1047, Université de Montpellier, Service de Microbiologie et Hygiène Hospitalière, CHU Nîmes, 30029 Nîmes, France.
Service de Microbiologie et Hygiène Hospitalière, CHU Nîmes, 30029 Nîmes, France.
Toxins (Basel). 2021 Apr 28;13(5):317. doi: 10.3390/toxins13050317.
Methicillin-resistant (MRSA) can cause chronic lung infections in patients with Cystic Fibrosis (CF). One option for managing them is the use of linezolid. We hereby report the in-host emergence of linezolid resistance (LR) in MRSA in CF siblings via a population analysis. A collection of 171 MRSA strains from 68 samples were characterized by determining their linezolid Minimal Inhibitory Concentrations (MICs), analyzing the locus of staphylococcal protein A () and whole genome sequencing. Courses of linezolid were retraced. Strains belonged to three types (t002, t045, t127) and two sequence types (ST1, ST5). Emergence of LR occurred under treatment, one year apart in both siblings, in the CC5-MRSA-I Geraldine clone harboring the toxic shock syndrome toxin-1-encoding gene. Resistance was related to a G2576T substitution present in a variable number of 23S rRNA gene copies. Susceptible and resistant strains were co-isolated within samples. Single Nucleotide Polymorphism-based analysis revealed complex colonizations by highly diversified, clonally related populations. LR remains rare in MRSA and there are very few longitudinal analyses documenting its emergence. Analyzing a large MRSA collection revealed new aspects of LR emergence: it emerges in specific subclonal lineages resulting from adaptive diversification of MRSA in the CF lung and this heterogeneity of intra-sample resistance may contribute to compromising antibiotic management.
耐甲氧西林金黄色葡萄球菌（MRSA）可导致囊性纤维化（CF）患者慢性肺部感染。管理方法之一是使用利奈唑胺。我们通过群体分析报告了 CF 兄弟姐妹中 MRSA 对利奈唑胺耐药（LR）的体内出现。从 68 个样本中收集了 171 株 MRSA 菌株，通过测定其利奈唑胺最小抑菌浓度（MIC）、分析葡萄球菌蛋白 A 基因座（）和全基因组测序来表征它们。追溯了利奈唑胺的疗程。菌株属于三个克隆型（t002、t045、t127）和两个序列型（ST1、ST5）。在携带毒性休克综合征毒素-1 编码基因的 CC5-MRSA-I 杰拉尔丁克隆中，LR 在一年后分别在两个兄弟姐妹的治疗中出现。耐药性与 23S rRNA 基因拷贝数中存在的 G2576T 取代有关。敏感和耐药菌株在样本内同时分离出来。基于单核苷酸多态性的分析显示，高度多样化、克隆相关的群体存在复杂的定植。LR 在 MRSA 中仍然很少见，并且很少有纵向分析记录其出现。分析大量的 MRSA 集合揭示了 LR 出现的新方面：它出现在特定的亚克隆谱系中，这些谱系是由于 CF 肺部中 MRSA 的适应性多样化而产生的，这种样本内耐药性的异质性可能会影响抗生素管理。
