| Title: | Structural and Genomic Evolution of RRNPPA Systems and Their Pheromone Signaling |
| Author(s): | Felipe-Ruiz A; Marina A; Rocha EPC; |
| Address: | "Instituto de Biomedicina de Valencia (IBV), CSIC and CIBER de Enfermedades Raras (CIBERER), Valencia, Spain. Institut Pasteur, Universite de Paris Cite, CNRS UMR3525, Microbial Evolutionary Genomics, Paris, France" |
| Abstract: | "In Firmicutes, important processes such as competence development, sporulation, virulence, and biofilm formation are regulated by cytoplasmic quorum sensing (QS) receptors of the RRNPPA family using peptide-based communication. Although these systems regulate important processes in a variety of bacteria, their origin and diversification are poorly understood. Here, we integrate structural, genomic, and phylogenetic evidence to shed light on RRNPPA protein origin and diversification. The family is constituted by seven different subfamilies with different domain architectures and functions. Among these, three were found in Lactobacillales (Rgg, ComR, and PrgX) and four in Bacillales (AimR, NprR, PlcR, and Rap). The patterns of presence and the phylogeny of these proteins show that subfamilies diversified a long time ago, resulting in key structural and functional differences. The concordance between the distribution of subfamilies and the bacterial phylogeny was somewhat unexpected, since many of the subfamilies are very abundant in mobile genetic elements, such as phages, plasmids, and phage-plasmids. The existence of diverse propeptide architectures raises intriguing questions about their export and maturation. It also suggests the existence of diverse roles for the RRNPPA systems. Some systems encode multiple pheromones on the same propeptide or multiple similar propeptides, suggesting that they act as 'chatterers.' Many others lack pheromone genes and may be 'eavesdroppers.' Interestingly, AimR systems without associated propeptide genes were particularly abundant in chromosomal regions not classed as prophages, suggesting that either the bacterium or other mobile elements are eavesdropping on phage activity. IMPORTANCE Quorum sensing (QS) is a mechanism of bacterial communication, coordinating important decisions depending on bacterial population. QS regulates important processes not only in bacterial behavior but also in genetic mobile elements and host-guest interactions. In Firmicutes, the most important family of QS receptors is the RRNPPA family. Despite the importance of such systems in microbiology, we know little about RRNPPA origin and diversification. In this work, the combination of sequence analysis and structural biology allowed us to identify a very large number of novel systems but also to class of them in functional families and thereby study of their origin and functional diversification. Moreover, peptide pheromone analysis revealed new and intriguing mechanisms of communication, such as 'eavesdropper' systems which only listen for the pheromone and 'chatterers' that take control of the communication in their microenvironment" |
| Keywords: | "Phylogeny *Bacterial Proteins/metabolism *Quorum Sensing/physiology Genomics Evolution, Molecular Peptides/metabolism Pheromones/metabolism Gene Expression Regulation, Bacterial RRNPPA family TPR domain peptide pheromone quorum sensing signal transduction;" |
| Notes: | "MedlineFelipe-Ruiz, Alonso Marina, Alberto Rocha, Eduardo P C eng Research Support, Non-U.S. Gov't 2022/10/20 mBio. 2022 Dec 20; 13(6):e0251422. doi: 10.1128/mbio.02514-22. Epub 2022 Oct 19" |
