Signatures of antagonistic pleiotropy in a bacterial flagellin epitope

Immune systems respond to “non-self” molecules termed microbe-associated molecular patterns (MAMPs). Microbial genes encoding MAMPs have adaptive functions and are thus evolutionarily conserved. In the presence of a host, these genes are maladaptive and drive antagonistic pleiotropy (AP) because they promote microbe elimination by activating immune responses. The role AP plays in balancing the functionality of MAMP-coding genes against their immunogenicity is unknown. To address this, we focused on an epitope of flagellin that triggers antibacterial immunity in plants. Flagellin is conserved because it enables motility. Here, we decode the immunogenic and motility profiles of this flagellin epitope and determine the spectrum of amino acid mutations that drives AP. We discover two synthetic mutational tracks that undermine the detection activities of a plant flagellin receptor. These tracks generate epitopes with either antagonist or weaker agonist activities. Finally, we find signatures of these tracks layered atop each other in natural Pseudomonads. [Display omitted] •A flagellin epitope controls Pseudomonas motility and triggers plant immunity•The A. thaliana flagellin receptor resiliently interacts with many epitope variants•Pseudomonas motility is under evolutionary pressure due to receptor activity•A. thaliana is mostly colonized by Pseudomonas that antagonize receptor activity A plant immune receptor has constrained Pseudomonas motility by influencing the evolution of a flagellin epitope. To demonstrate this, Parys et al. interrogated thousands of physical interactions between the receptor and mutated epitopes and generated hundreds of synthetic bacterial strains to assess the impact of epitope mutations on motility.