Abstract
Constantly surrounded by kin or alien organisms in nature, eukaryotes and prokaryotes developed various communication systems to coordinate adaptive multi-entity behavior. In complex and overcrowded environments, they require to discriminate relevant signals in a myriad of pheromones to execute appropriate responses. In the human gut commensal Streptococcus salivarius, the cytoplasmic Rgg/RNPP regulator ComR couples competence to bacteriocin-mediated predation. Here, we describe a paralogous sensor duo, ScuR and SarF, which circumvents ComR in order to disconnect these two physiological processes. We highlighted the recurring role of Rgg/RNPP in the production of antimicrobials and designed a robust genetic screen to unveil potent/optimized peptide pheromones. Further mutational and biochemical analyses dissected the modifiable selectivity toward their pheromone and operating sequences at the subtle molecular level. Additionally, our results highlight how we might mobilize antimicrobial molecules while silencing competence in endogenous populations of human microflora and temper gut disorders provoked by bacterial pathogens.
Highlights
IntroductionAll organisms are parts of multi-species ecosystems. Some niches such as the human digestive tract are densely populated with more than 1000 species interacting with each other through competition or cooperation for nutrients and colonization areas (Huang et al, 2011; Kommineni et al, 2015; The Human Microbiome Project Consortium, 2012)
In the living world, all organisms are parts of multi-species ecosystems
The direct regulation of bacteriocins by ComR in the S. salivarius species is uncommon and suggests a positive selection for species-specific strategies that participate in niche adaptation (Mignolet et al, 2018)
Summary
All organisms are parts of multi-species ecosystems. Some niches such as the human digestive tract are densely populated with more than 1000 species interacting with each other through competition or cooperation for nutrients and colonization areas (Huang et al, 2011; Kommineni et al, 2015; The Human Microbiome Project Consortium, 2012). Metazoan and unicellular organisms developed social skills and set up kin, interspecies and even interkingdom trans-communication via pheromones (Hughes and Sperandio, 2008; Kholodenko, 2006; Waters and Bassler, 2005). This kind of behavior favors the coordination of cellular processes to provide a concerted response. In bacteria, this results in the production of defense/assault molecules targeting microorganisms or host immune cells, sporulation, mass locomotion, biofilm formation or acquisition of new genetic material (Waters and Bassler, 2005).
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