Diverse Sensory Repertoire of Paralogous Chemoreceptors Tlp2, Tlp3, and Tlp4 in Campylobacter Jejuni.

Campylobacter jejuni responds to extracellular stimuli via transducer-like chemoreceptors (Tlps). Here, we describe receptor-ligand interactions of a unique paralogue family of dCache_1 (double Calcium channels and chemotaxis) chemoreceptors: Tlp2, Tlp3, and Tlp4. Phylogenetic analysis revealed that Tlp2, Tlp3, and Tlp4 receptors may have arisen through domain duplications, followed by a divergent evolutionary drift, with Tlp3 emerging more recently, and unexpectedly, responded to glycans, as well as multiple organic and amino acids with overlapping specificities. All three Tlps interacted with five monosaccharides and complex glycans, including Lewis's antigens, P antigens, and fucosyl GM1 ganglioside, indicating a potential role in host-pathogen interactions. Analysis of chemotactic motility of single, double, and triple mutants indicated that these chemoreceptors are likely to work together to balance responses to attractants and repellents to modulate chemotaxis in C. jejuni. Molecular docking experiments, in combination with saturation transfer difference nuclear magnetic resonance spectroscopy and competition surface plasmon resonance analysis, illustrated that the ligand-binding domain of Tlp3 possess one major binding pocket with two overlapping, but distinct binding sites able to interact with multiple ligands. A diverse sensory repertoire could provide C. jejuni with the ability to modulate responses to attractant and repellent signals and allow for adaptation in host-pathogen interactions. IMPORTANCE Campylobacter jejuni responds to extracellular stimuli via transducer-like chemoreceptors (Tlps). This remarkable sensory perception mechanism allows bacteria to sense environmental changes and avoid unfavorable conditions or to maneuver toward nutrient sources and host cells. Here, we describe receptor-ligand interactions of a unique paralogue family of chemoreceptors, Tlp2, Tlp3, and Tlp4, that may have arisen through domain duplications, followed by a divergent evolutionary drift, with Tlp3 emerging more recently. Unlike previous reports of ligands interacting with sensory proteins, Tlp2, Tlp3, and Tlp4 responded to many types of chemical compounds, including simple and complex sugars such as those present on human blood group antigens and gangliosides, indicating a potential role in host-pathogen interactions. Diverse sensory repertoire could provide C. jejuni with the ability to modulate responses to attractant and repellent signals and allow for adaptation in host-pathogen interactions.