Homeostatic Interplay between Bacterial Cell-Cell Signaling and Iron in Virulence

PLoS Pathogens

Biliana Lesic¹  Valérie Dekimpe¹  Jianxin He¹  François Lépine¹  Laurence G. Rahme²  Yiorgos Apidianakis²  Gaoping Xiao²  Ronen Hazan²  Eric Déziel²  Christos Astrakas³ 

[1] Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, Massachusetts, United States of America;Department of Surgery, Harvard Medical School and Massachusetts General Hospital, Boston, Massachusetts, United States of America;INRS-Institut Armand-Frappier, Laval, Québec, Canada

关键词: Pseudomonas aeruginosa;    Gene expression;    Operons;    Gene regulation;    Regulons;    Virulence factors;    Regulator genes;    Signaling molecules;   

DOI  :  10.1371/journal.ppat.1000810

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Pathogenic bacteria use interconnected multi-layered regulatory networks, such as quorum sensing (QS) networks to sense and respond to environmental cues and external and internal bacterial cell signals, and thereby adapt to and exploit target hosts. Despite the many advances that have been made in understanding QS regulation, little is known regarding how these inputs are integrated and processed in the context of multi-layered QS regulatory networks. Here we report the examination of the Pseudomonas aeruginosa QS 4-hydroxy-2-alkylquinolines (HAQs) MvfR regulatory network and determination of its interaction with the QS acyl-homoserine-lactone (AHL) RhlR network. The aim of this work was to elucidate paradigmatically the complex relationships between multi-layered regulatory QS circuitries, their signaling molecules, and the environmental cues to which they respond. Our findings revealed positive and negative homeostatic regulatory loops that fine-tune the MvfR regulon via a multi-layered dependent homeostatic regulation of the cell-cell signaling molecules PQS and HHQ, and interplay between these molecules and iron. We discovered that the MvfR regulon component PqsE is a key mediator in orchestrating this homeostatic regulation, and in establishing a connection to the QS rhlR system in cooperation with RhlR. Our results show that P. aeruginosa modulates the intensity of its virulence response, at least in part, through this multi-layered interplay. Our findings underscore the importance of the homeostatic interplay that balances competition within and between QS systems via cell-cell signaling molecules and environmental cues in the control of virulence gene expression. Elucidation of the fine-tuning of this complex relationship offers novel insights into the regulation of these systems and may inform strategies designed to limit infections caused by P. aeruginosa and related human pathogens.

【 授权许可】

CC BY