Detection and analysis of methicillin-resistant human-adapted sequence type 398 allows insight into community-associated methicillin-resistant Staphylococcus aureus evolution.
Detection and analysis of methicillin-resistant human-adapted sequence type 398 allows insight into community-associated methicillin-resistant Staphylococcus aureus evolution.
复制标题
检测和分析耐甲氧西林人类适应序列 398 型可深入了解群落相关的耐甲氧西林金黄色葡萄球菌进化
DOI：
10.1186/s13073-018-0514-9
复制
发表时间：
2018-01-29
期刊：
影响因子：
12.3
通讯作者：
Li M
中科院分区：
文献类型：
--
作者：
He L;Zheng HX;Wang Y;Le KY;Liu Q;Shang J;Dai Y;Meng H;Wang X;Li T;Gao Q;Qin J;Lu H;Otto M;Li M
高毒力社区相关耐甲氧西林金黄色葡萄球菌（CA-MRSA）的严重感染是一个全球性问题。然而，定义CA-MRSA进化的分子事件仍然知之甚少。已知序列类型（ST）398的MRSA经常感染牲畜，而感染人类的ST 398分离株通常是甲氧西林敏感的或代表源自牲畜相关（LA）-MRSA的MRSA。我们使用新检测到的CA-MRSA ST 398分离株的全基因组测序，与地理上匹配的LA-MRSA和甲氧西林敏感的ST 398进行比较，以确定它们的进化历史。此外，我们使用包括动物感染模型在内的表型分析来深入了解这些CA-MRSA分离株的毒力演变。最后，我们确定了甲氧西林耐药性和甲氧西林耐药基因mecA及其青霉素结合蛋白产物PBP 2a在大量不同ST的CA-MRSA菌株中的表达。我们报告了几例严重和致命的感染，由于ST 398 CA-MRSA。相关分离株显示了人类适应性甲氧西林敏感性ST 398的典型遗传特征。全基因组测序表明，它们在几个不同的场合从人类适应的，甲氧西林敏感的克隆进化而来。重要的是，与其甲氧西林敏感的前辈相比，分离株没有发生一致的遗传变异或毒力变化。最后，我们观察到显着和一致性较低的甲氧西林耐药性和耐药基因mecA的表达，与医院相关的MRSA菌株相比，在一个多样化的选择CA-MRSA菌株。我们的研究提供了从甲氧西林敏感的前体中开发高毒力的人适应性ST 398 CA-MRSA分离株的证据。值得注意的是，我们的调查表明，与广泛的观念相反，CA-MRSA的发展不一定与特定毒力基因的获得或其他增加毒力的变化有关。相反，我们的研究结果强调了CA-MRSA特征性葡萄球菌盒式染色体mec类型的重要性，这种类型仅提供低水平的甲氧西林耐药性。我们的研究结果对于CA-MRSA的诊断特别重要，因为它们表明特定毒力基因的存在通常不能用于该目的。本文的在线版本（doi：10.1186/s13073-018-0514-9）包含补充材料，可供授权用户使用。
Severe infections with highly virulent community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) are a global problem. However, the molecular events defining the evolution of CA-MRSA are still poorly understood. MRSA of sequence type (ST) 398 is known to frequently infect livestock, while ST398 isolates infecting humans are commonly methicillin-susceptible or represent MRSA originating from livestock-associated (LA)-MRSA. We used whole genome sequencing of newly detected CA-MRSA ST398 isolates, in comparison to geographically matched LA-MRSA and methicillin-sensitive ST398, to determine their evolutionary history. Furthermore, we used phenotypic analyses including animal infection models to gain insight into the evolution of virulence in these CA-MRSA isolates. Finally, we determined methicillin resistance and expression of the methicillin resistance-conferring gene mecA and its penicillin-binding protein product, PBP2a, in a large series of CA-MRSA strains of divergent STs. We report several cases of severe and fatal infections due to ST398 CA-MRSA. The responsible isolates showed the typical genetic characteristics reported for human-adapted methicillin-sensitive ST398. Whole genome sequencing demonstrated that they evolved from human-adapted, methicillin-susceptible clones on several different occasions. Importantly, the isolates had not undergone consistent genetic alterations or changes in virulence as compared to their methicillin-susceptible predecessors. Finally, we observed dramatically and consistently lower methicillin resistance and expression of the resistance gene mecA, as compared to hospital-associated MRSA strains, in a diverse selection of CA-MRSA strains. Our study presents evidence for the development of highly virulent human-adapted ST398 CA-MRSA isolates from methicillin-susceptible predecessors. Notably, our investigation indicates that, in contrast to widespread notions, the development of CA-MRSA is not necessarily associated with the acquisition of specific virulence genes or other virulence-increasing changes. Rather, our findings emphasize the importance of the CA-MRSA-characteristic staphylococcal cassette chromosome mec types, which provide only low-level methicillin resistance, for that process. Our findings are of particular importance for the diagnosis of CA-MRSA, inasmuch as they indicate that the presence of specific virulence genes cannot generally be used for that purpose. The online version of this article (doi:10.1186/s13073-018-0514-9) contains supplementary material, which is available to authorized users.