A 3'UTR-derived small RNA represses pneumolysin synthesis and facilitates pneumococcal brain invasion.

Autor: Shen K; State Key Laboratory of Microbial Resources, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.; University of Chinese Academy of Sciences, Beijing, China., Miao W; State Key Laboratory of Microbial Resources, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.; School of Basic Medicine, Shenyang Medical College, Shenyang, China., Zhu L; State Key Laboratory of Microbial Resources, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.; University of Chinese Academy of Sciences, Beijing, China., Hu Q; State Key Laboratory of Microbial Resources, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.; University of Chinese Academy of Sciences, Beijing, China., Ren F; School of Basic Medicine, Shenyang Medical College, Shenyang, China., Dong X; State Key Laboratory of Microbial Resources, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China. dongxz@im.ac.cn.; University of Chinese Academy of Sciences, Beijing, China. dongxz@im.ac.cn., Tong H; State Key Laboratory of Microbial Resources, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China. tonghuichun@im.ac.cn.; University of Chinese Academy of Sciences, Beijing, China. tonghuichun@im.ac.cn.
Jazyk: angličtina
Zdroj: Communications biology [Commun Biol] 2024 Sep 13; Vol. 7 (1), pp. 1130. Date of Electronic Publication: 2024 Sep 13.
DOI: 10.1038/s42003-024-06845-8
Abstrakt: Pneumolysin (Ply) of Streptococcus pneumoniae (pneumococcus) at relatively high and low levels facilitates pneumococcal invasion into the lung and brain, respectively; however, the regulatory mechanisms of Ply expression are poorly understood. Here, we find that a small RNA plyT, processed from the 3'UTR of the ply operon, is expressed higher in anaerobically- than in statically-cultured pneumococcus D39. Using bioinformatic, biochemical and genetic approaches, we reveal that PlyT inhibits Ply synthesis and hemolytic activities by pairing with an RBS-embedded intergenic region of the ply operon. The RNA-binding protein SPD_1558 facilitates the pairing. Importantly, PlyT inhibition of Ply synthesis is stronger in anaerobic culture and leads to lower Ply abundance. Deletion of plyT decreases the number of pneumococci in the infected mouse brain and reduces the virulence, demonstrating that PlyT-regulated lower Ply in oxygen-void microenvironments, such as the blood, is important for pneumococcus to cross the blood-brain barrier and invade the brain. PlyT-mediated repression of Ply synthesis at anoxic niches is also verified in pneumococcal serotype 4 and 14 strains; moreover, the ply operon with a 3'UTR-embedded plyT, and the pairing sequences of IGR and plyT are highly conserved among pneumococcal strains, implying PlyT-regulated Ply synthesis might be widely employed by pneumococcus.
(© 2024. The Author(s).)
Databáze: MEDLINE
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