A Non-Coding RNA Promotes Bacterial Persistence and Decreases Virulence by Regulating a Regulator in Staphylococcus aureus

PLoS Pathogens

Cédric Romilly¹  Thomas Geissmann¹  Sandrine Boisset¹  Pascale Romby²  Claire Lays²  Philippe Hammann³  Isabelle Caldelari⁴  Arnaud Tomasini⁵  François Vandenesch⁵  Yvonne Benito⁶ 

[1] Architecture et Réactivité de l'ARN, Université de Strasbourg, CNRS, IBMC, Strasbourg, France;CIRI, International Center for Infectiology Research, Université de Lyon, Lyon, France;CNRS, UMR5308, Lyon, France;Ecole Normale Supérieure de Lyon, Lyon, France;Inserm U1111, Lyon, France;Université Lyon 1, Lyon, France

关键词: Messenger RNA;    Mutant strains;    Staphylococcus aureus;    Ribonucleases;    Bacterial biofilms;    Biofilms;    Catheters;    Protein translation;   

DOI  :  10.1371/journal.ppat.1003979

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Staphylococcus aureus produces a high number of RNAs for which the functions are poorly understood. Several non-coding RNAs carry a C-rich sequence suggesting that they regulate mRNAs at the post-transcriptional level. We demonstrate that the Sigma B-dependent RsaA RNA represses the synthesis of the global transcriptional regulator MgrA by forming an imperfect duplex with the Shine and Dalgarno sequence and a loop-loop interaction within the coding region of the target mRNA. These two recognition sites are required for translation repression. Consequently, RsaA causes enhanced production of biofilm and a decreased synthesis of capsule formation in several strain backgrounds. These phenotypes led to a decreased protection of S. aureus against opsonophagocytic killing by polymorphonuclear leukocytes compared to the mutant strains lacking RsaA. Mice animal models showed that RsaA attenuates the severity of acute systemic infections and enhances chronic catheter infection. RsaA takes part in a regulatory network that contributes to the complex interactions of S. aureus with the host immune system to moderate invasiveness and favour chronic infections. It is the first example of a conserved small RNA in S. aureus functioning as a virulence suppressor of acute infections. Because S. aureus is essentially a human commensal, we propose that RsaA has been positively selected through evolution to support commensalism and saprophytic interactions with the host.

【 授权许可】

CC BY