Chen Yiyi, Zhu Feiteng, Hong Yueqin, Liu Yeqiong, Wang Haiping, Jiang Shengnan, Chen Mengzhen, Ji Shujuan, Wang Zhengan, Yu Yunsong, Chen Yan, Sun Lu
Center for General Practice Medicine, Department of Infectious Diseases, Zhejiang Provincial People's Hospital (Affiliated People's Hospital), Hangzhou Medical College, Hangzhou, China.
Department of Infectious Diseases, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China.
mSystems. 2025 Jul 22;10(7):e0028225. doi: 10.1128/msystems.00282-25. Epub 2025 Jun 27.
is a major pathogen responsible for hospital- and community-acquired infections, with the accessory gene regulator () system playing a central role in virulence control. The ST9 lineage commonly associated with livestock exhibits multidrug resistance but remains understudied in terms of virulence. In this work, we examined nine clinical ST9 methicillin-resistant isolates and identified two strains carrying spontaneous frameshift mutations in the locus, resulting in the loss of RNAIII and α-toxin expression. These -deficient strains exhibited reduced hemolytic activity, enhanced biofilm formation, and attenuated virulence in a infection model. These preliminary pieces of evidence suggested a critical role of the system in ST9 virulence. Comparative genomic analyses revealed distinct pathogenicity islands in ST9, differing from those in other common clinical lineages. Notably, we identified three novel prophage islands (φST9-A, φST9-B, and φST9-C), with φST9-B carrying the recently characterized virulence gene, suggesting that recombination events within livestock-associated MRSA could contribute to the genetic diversification of ST9. These findings demonstrate the significant virulence potential of the ST9 lineage and the importance of -mediated regulation. Moreover, the presence of new prophages highlights the evolutionary adaptability of this lineage. Collectively, our results underscore the clinical threat posed by ST9 MRSA and the necessity for vigilant monitoring to control its spread.IMPORTANCEMethicillin-resistant (MRSA) ST9 commonly associated with livestock remains understudied in terms of virulence mechanisms. This study identifies key insights into ST9 MRSA virulence, focusing on the accessory gene regulator () system, which regulates virulence in . We show that -deficient ST9 strains exhibit altered virulence phenotypes, including reduced hemolysis and increased biofilm formation. Additionally, our genomic analysis reveals novel prophage islands in ST9, highlighting the lineage's genetic adaptability and potential for increased virulence. These findings emphasize the need for continued surveillance and targeted strategies to control the spread of ST9 MRSA, with important implications for diagnostic and therapeutic approaches.
是医院获得性感染和社区获得性感染的主要病原体，辅助基因调节子（）系统在毒力控制中起核心作用。通常与家畜相关的ST9谱系表现出多重耐药性，但在毒力方面仍未得到充分研究。在这项工作中，我们检查了9株临床ST9耐甲氧西林分离株，发现两株在基因座上携带自发移码突变，导致RNAIII和α-毒素表达缺失。这些缺陷菌株在感染模型中表现出溶血活性降低、生物膜形成增强和毒力减弱。这些初步证据表明系统在ST9毒力中起关键作用。比较基因组分析揭示了ST9中不同的致病岛，与其他常见临床谱系中的致病岛不同。值得注意的是，我们鉴定出三个新的噬菌体岛（φST9-A、φST9-B和φST9-C），其中φST9-B携带最近鉴定的毒力基因，表明家畜相关耐甲氧西林金黄色葡萄球菌内的重组事件可能有助于ST9的遗传多样化。这些发现证明了ST9谱系的显著毒力潜力以及介导调节的重要性。此外，新噬菌体的存在突出了该谱系的进化适应性。总的来说，我们的结果强调了ST9耐甲氧西林金黄色葡萄球菌带来的临床威胁以及警惕监测以控制其传播的必要性。重要性与家畜相关的耐甲氧西林金黄色葡萄球菌（MRSA）ST9在毒力机制方面仍未得到充分研究。本研究确定了对ST9 MRSA毒力的关键见解，重点关注调节毒力的辅助基因调节子（）系统。我们表明，缺陷的ST9菌株表现出改变的毒力表型，包括溶血减少和生物膜形成增加。此外，我们的基因组分析揭示了ST9中的新噬菌体岛，突出了该谱系的遗传适应性和毒力增加的潜力。这些发现强调了持续监测和针对性策略以控制ST9 MRSA传播的必要性，对诊断和治疗方法具有重要意义。
