Self-recognition signaling and ecological variation in the bacterial pathogen Proteus mirabilis

Abstract

Considering molecular interactions within the cell and with the environment can advance our understanding of opportunistic pathogens within a framework of ecology and evolution. For the opportunistic pathogen Proteus mirabilis, self recognition impacts swarming, a collective motility associated with virulence. During swarming, neighboring cells inject an identity protein that induces a stress response and iteratively excludes non-kin cells. The interactions of Ids signaling within the cell and the broader ecology of collective behavior were previously unknown. During my dissertation research, I showed that a conserved serine transporter, SdaC, is the dominant serine transporter during swarming and essential for self recognition. Analysis of SdaC single-residue variants and homologs revealed that the open conformation of SdaC is necessary and sufficient for self recognition and is conserved in SdaC from Escherichia coli but not the similar serine transporter YhaO in P. mirabilis. We hypothesize that a specific molecular interface is likely exposed when SdaC is in an open conformation that facilitates inner membrane integration of the injected identity protein. Notably, the majority of sequenced P. mirabilis isolates share SdaC and self-recognition factors, whether found in infections or from animal or environmental reservoirs, raising questions about the phylogenetic history of P. mirabilis. To address this gap, we performed whole-genome sequencing and behavioral characterizations of asymptomatic animal-associated P. mirabilis strains. We found that genes for virulence and swarming are in the core genome, while identity proteins are in the non-core. Further, I showed that poor swarmers were attenuated in virulence and, in one case, this phenotype could be traced to a nonsense mutation in the flagellar gene fliF. Our approach, using diverse isolates and natural variation, uncovered unexpected ecotype similarity, opening a path to identify new molecular mechanisms of virulence.