Identification and characterisation of bacterial TIR domains, with particular focus on yersinia pestis: Study Data

After an initial screen of their activity, a Tdp from Yersinia pestis, the causative agent of plague, was down-selected for further investigation. The bioinformatic analysis found a high representation of Tdps in bacteria generally classified as non-pathogens, and that TIR domains are promiscuous in their co-occurrence with other domains. This analysis also showed that they are not necessarily conserved between strains and species.

These findings question the universal role of Tdps in the pathogenic evasion of a host immune response and suggest they may have other functions. Initial screening of down-selected Tdps showed that they were able to modulate immune signalling pathways in vitro, but studies with a Tdp-deficient mutant of Y. pestis did not demonstrate a role for this protein in the virulence of Y. pestis in a mouse model. However, this Tdp-deficient mutant did display two characteristics in vitro: an increased autoaggregation phenotype when compared to wild-type Y. pestis and an inability to survive as well as wild-type bacteria in conditions of high salinity.

These fmdings indicate that TIR domain proteins may have other roles in bacterial physiology unrelated to immune evasion.