Liang Zijing, Wang Shuoyue, Zhu Xinchi, Ma Jiale, Yao Huochun, Wu Zongfu
MOE Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, China.
Key Lab of Animal Bacteriology, Ministry of Agriculture, Nanjing, China.
Virulence. 2025 Dec;16(1):2491635. doi: 10.1080/21505594.2025.2491635. Epub 2025 Apr 16.
is a Gram-positive pathogen causing septicaemia and meningitis in pigs and humans. However, how maintains a high bacterial load in the blood and brain is poorly understood. In this study, we found that a small RNA rss03 is predominantly present in , , and , implying a conserved biological function. rss03 with a size of 303 nt mainly exists in sequence type (ST) 1 and epidemic ST7 strains that are responsible for human infections in China. Using MS2-affinity purification coupled with RNA sequencing (MAPS), proteomics analysis, and CopraRNA prediction, 14 direct targets of rss03 from an ST7 strain were identified. These direct targets mainly involve substance transport, transcriptional regulation, rRNA modification, and stress response. A more detailed analysis reveals that rss03 interacts with the coding region of mRNA, and unexpectedly rss03 protects mRNA from degradation by RNase J1. The GlpF protein is an aquaporin, contributes to oxidative stress resistance by HO efflux, and facilitates bacterial survival in murine macrophages RAW264.7. Finally, we showed that rss03 and GlpF are required to maintain a high bacterial load in mouse blood and brain. Our study presents the first sRNA targetome in streptococci, enriches the knowledge of sRNA regulation in streptococci, and identifies pathways contributing to pathogenesis.
是一种革兰氏阳性病原体，可导致猪和人类患败血症和脑膜炎。然而，人们对其如何在血液和大脑中维持高细菌载量知之甚少。在本研究中，我们发现一种小RNA rss03主要存在于[具体菌种]、[具体菌种]和[具体菌种]中，这意味着它具有保守的生物学功能。大小为303 nt的rss03主要存在于序列型（ST）1和流行的ST7菌株中，这些菌株在中国导致人类感染。使用MS2亲和纯化结合RNA测序（MAPS）、蛋白质组学分析和CopraRNA预测，从一株ST7菌株中鉴定出rss03的14个直接靶点。这些直接靶点主要涉及物质转运、转录调控、rRNA修饰和应激反应。更详细的分析表明，rss03与[具体基因]mRNA的编码区相互作用，并且出乎意料的是，rss03保护[具体基因]mRNA不被RNase J1降解。GlpF蛋白是一种水通道蛋白，通过水外流有助于[具体菌种]抵抗氧化应激，并促进细菌在小鼠巨噬细胞RAW264.7中存活。最后，我们表明rss03和GlpF是在小鼠血液和大脑中维持高细菌载量所必需的。我们的研究展示了链球菌中的首个sRNA靶标组，丰富了链球菌中sRNA调控的知识，并确定了有助于[具体菌种]致病的途径。
