Linking Self Versus Non-Self Recognition Genes and Their Function to Microbial Community Structure

Abstract

Many bacterial species reside in dense communities, such as the gut and oral microbiomes, which retain a structural organization where genetically similar bacterial populations are physically separated. Key candidates for the organization of such structures are contact-dependent interactions, because these structures involve cell contact. These interactions can be competitive, as bacteria will be competing for the same resources. Bacteria use various secretion systems to deliver toxins or effector proteins into neighboring cells in a contact-dependent manner. Cells producing toxins have a competitive advantage by inhibiting growth of neighboring cells. The production of a strain-specific immunity protein by the recipient cell can counteract the effects of the toxin, making these interactions a form of self-recognition. Using biochemical and genetic approaches, I elucidated the target of the Proteus mirabilis BB2000-derived toxin, IdrD, and its immunity protein, IdrE. The C-terminal domain of IdrD functions as a DNase; IdrE counteracts this activity and causes loss of toxin signal by an unknown mechanism. The same molecular function was observed in the homologous toxin-immunity pair in the bacterium Rothia aeria C6B, which is distantly related to P. mirabilis. The molecular characterization was combined with metagenomic analysis. We are able to probe for the abundance of these toxin-immunity pairs in different communities, and even detect subdomains within the toxin. Combining molecular characterization with metagenomic analysis provides a way to study toxin-immunity pairs in the context of a microbial community.