The puzzle of TIR domain-containing proteins in bacteria (43.3)

Abstract

Abstract Toll/interleukin-1 receptor (TIR) domain-containing proteins play important roles in defense against pathogens in both animals and plants, connecting the immunity signaling pathways via a chain of specific protein-protein interactions. Among them is SARM, the only TIR domain-containing adaptor that can negatively regulate TLR signaling. By extensive phylogenetic analysis, we show here that SARM clusters with bacterial TIR domains, suggesting a relatively recent lateral gene transfer from bacteria to animals. We also show evidence of several additional, independent transfer events, none of which, however, survived in vertebrates. TIR domain-containing proteins had been characterized in bacterial pathogens, where they were shown to represent a new class of virulence factors that can suppress animal Toll-like receptor (TLR) dependent host defenses. An evolutionary relationship between the animal SARM adaptor and bacterial proteins with TIR domains illustrates the possible role that bacterial TIR-containing proteins play in regulating eukaryotic immune responses and how this mechanism was possibly adapted by the eukaryotes themselves.