Determinants governing ligand specificity of the Vibrio harveyi LuxN quorum‐sensing receptor

Abstract

Summary Quorum sensing is a process of bacterial cell-cell communication that relies on the production, release, and receptor-driven detection of extracellular signal molecules called autoinducers. The quorum-sensing bacterium Vibrio harveyi exclusively detects the autoinducer N-((R)-3-hydroxybutanoyl)-L-homoserine lactone (3OH-C4 HSL) via the two-component receptor LuxN. To discover the principles underlying the exquisite selectivity LuxN has for its ligand, we identified LuxN mutants with altered specificity. LuxN uses three mechanisms to verify that the bound molecule is the correct ligand: In the context of the overall ligand-binding site, His210 validates the C3 modification, Leu166 surveys the chain-length, and a strong steady-state kinase bias imposes an energetic hurdle for inappropriate ligands to elicit signal transduction. Affinities for the LuxN Kinaseon and Kinaseoff states underpin whether a ligand will act as an antagonist or an agonist. Mutations that bias LuxN to the agonized, Kinaseoff, state are clustered in a region adjacent to the ligand-binding site, suggesting that this region acts as the switch that triggers signal transduction. Together, our analyses illuminate how a histidine sensor kinase differentiates between ligands and exploits those differences to regulate its signaling activity.

Facultative cheating supports the coexistence of diverse quorum-sensing alleles

“…From an ecological perspective, facultative interactions can occur between different species in a multispecies population, and these may explain some of the diversity found in microbial communities (48). Recent work has demonstrated the ecological richness that can be attained by the chemical diversity of antibiotic production and degradation (49,50).…”

Quorum sensing signal–response systems in Gram-negative bacteria

“…Bacteria that live in heterogeneous populations presumably encounter complex mixtures of autoinducers that are produced by themselves, their clonal siblings, close relatives, and their non-kin neighbours, which could be fierce competitors 7,12,13 . Thus, bacteria face the challenge of extracting information from mixtures of related and unrelated molecules.…”

A Host-Produced Autoinducer-2 Mimic Activates Bacterial Quorum Sensing

“…Quorum-sensing autoinducers can confer species-specific communication, genera-wide communication, and species-non-specific communication, suggesting that autoinducers encode information about the number of bacteria in the vicinal community, as well as information about whether neighboring cells are closely or distantly related (Bassler et al, 1993, Schauder et al, 2001, Henke and Bassler, 2004, Ng and Bassler, 2009, Ke et al, 2015). Enteric bacteria engage in quorum-sensing activities including polysaccharide matrix production, biofilm formation, and exo-enzyme production, hallmark behaviors deployed by bacteria when colonizing complex environments such as the gut (Taga and Bassler, 2003, Xavier et al, 2007).…”