Jin Ye, Gao Chenyang, Teng Gaoqin, Zhou Zhenchao, Zhou Wangxiao, Huang Man
Department of General Intensive Care Unit, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang, People's Republic of China.
Key Laboratory of Early Warning and Intervention of Multiple Organ Failure, China National Ministry of Education, Hangzhou, Zhejiang, People's Republic of China.
mSystems. 2024 Dec 17;9(12):e0114224. doi: 10.1128/msystems.01142-24. Epub 2024 Nov 12.
sequence type (ST) 88, encompassing both methicillin-resistant (MRSA) and methicillin-sensitive (MSSA) phenotypes, is globally prevalent and commonly associated with skin and soft tissue infections. Despite its widespread occurrence, comprehensive genomic studies on this clone remain scarce. In this study, we performed detailed genomic analyses on 130 ST88 isolates derived from severe bloodstream infections alongside 275 publicly available ST88 sequences. Our phylogenetic analysis identified four distinct clades, with evidence suggesting independent evolution and significant clonal expansion of ST88 in China, particularly within clade I, which appeared to have emerged circa 1964. We documented notable interregional, international, and even intercontinental transmission of ST88 isolates. Variability in the distribution of SCC and types was observed across clades. Our analyses indicated distinct patterns in the distribution of resistance genes, virulence genes, and mobile genetic elements among the clades, with clade I notably harboring the highest prevalence of the intact gene and an independently acquired novel prophage, φST88-1. Conversely, clade IV exhibited deletions within the gene, with certain sub-clades lacking the and genes, underscoring the superior adhesive capabilities of clade I. experiments confirmed enhanced biofilm formation in clade I isolates, although the levels of hemolysis and cytotoxicity were similar across clades. Pan-genome-wide association study revealed that core SNPs, rather than the accessory genome, are the primary contributors to the diversification of the ST88 clades. These findings enrich our understanding of the genetic foundations underpinning the transmission dynamics and phenotypic diversity of ST88 clones globally.IMPORTANCEUnderstanding the evolution and transmission of ST88 clones is critically important due to their spread within food, hospital, and community environments, leading to significant health issues. Despite its prevalence, detailed genomic insights into ST88, particularly regarding its diversity and evolutionary dynamics, have been lacking. Our comprehensive genomic analysis of 130 ST88 isolates from severe bloodstream infections, alongside 275 sequences from public databases, significantly advances our understanding of this pathogen. We identified four distinct evolutionary clades, demonstrating the independent evolution and substantial clonal expansion of ST88 in China, as well as its ability to spread across regions and continents. The diversity among the isolates was evident in their unique profiles of elements, antibiotic resistance genes, virulence genes, and mobile genetic elements. Our findings underscore the critical role of core genomic variations over accessory elements in driving the diversification of ST88. This enhanced understanding provides new insights that could inform more effective control strategies, crucial for developing interventions to combat the global spread of this formidable pathogen.
序列类型(ST)88,包括耐甲氧西林(MRSA)和甲氧西林敏感(MSSA)表型,在全球普遍存在,通常与皮肤和软组织感染相关。尽管其广泛存在,但对该克隆的全面基因组研究仍然很少。在本研究中,我们对130株源自严重血流感染的ST88分离株以及275条公开可用的ST88序列进行了详细的基因组分析。我们的系统发育分析确定了四个不同的进化枝,有证据表明ST88在中国独立进化并显著克隆扩张,特别是在进化枝I中,其似乎在1964年左右出现。我们记录了ST88分离株显著的区域间、国际间甚至洲际传播。观察到葡萄球菌盒式染色体(SCC)和类型在各进化枝中的分布存在差异。我们的分析表明,各进化枝中耐药基因、毒力基因和可移动遗传元件的分布模式不同,进化枝I中完整的葡萄球菌蛋白A(spa)基因和一个独立获得的新型前噬菌体φST88 - 1的流行率显著最高。相反,进化枝IV在spa基因内存在缺失,某些亚进化枝缺乏fnbA和fnbB基因,突出了进化枝I更强的黏附能力。体外实验证实进化枝I分离株生物膜形成增强,尽管各进化枝的溶血和细胞毒性水平相似。全基因组关联研究表明,核心单核苷酸多态性(SNPs)而非辅助基因组是ST88进化枝多样化的主要贡献因素。这些发现丰富了我们对全球ST88克隆传播动态和表型多样性的遗传基础的理解。
重要性
了解ST88克隆的进化和传播至关重要,因为它们在食品、医院和社区环境中传播,导致重大健康问题。尽管其普遍存在,但对ST88的详细基因组见解,特别是关于其多样性和进化动态的见解一直缺乏。我们对130株来自严重血流感染的ST88分离株以及来自公共数据库的275条序列进行的全面基因组分析,极大地推进了我们对这种病原体的理解。我们确定了四个不同的进化枝,证明了ST88在中国的独立进化和大量克隆扩张,以及它在不同地区和各大洲传播的能力。分离株之间的多样性在其独特的葡萄球菌盒式染色体元件、抗生素耐药基因、毒力基因和可移动遗传元件谱中很明显。我们的发现强调了核心基因组变异而非辅助元件在推动ST88多样化中的关键作用。这种加深的理解提供了新的见解,可为更有效的控制策略提供依据,这对于制定干预措施以对抗这种强大病原体的全球传播至关重要。