Molecular Recognition by a Polymorphic Cell Surface Receptor Governs Cooperative Behaviors in Bacteria

Abstract

Cell-cell recognition is a fundamental process that allows cells to coordinate multicellular behaviors. Some microbes, such as myxobacteria, build multicellular fruiting bodies from free-living cells. However, how bacterial cells recognize each other by contact is poorly understood. Here we show that myxobacteria engage in recognition through interactions between TraA cell surface receptors, which leads to the fusion and exchange of outer membrane (OM) components. OM exchange is shown to be selective among 17 environmental isolates, as exchange partners parsed into five major recognition groups. TraA is the determinant of molecular specificity because: (i) exchange partners correlated with sequence conservation within its polymorphic PA14-like domain and (ii) traA allele replacements predictably changed partner specificity. Swapping traA alleles also reprogrammed social interactions among strains, including the regulation of motility and conferred immunity from inter-strain killing. We suggest that TraA helps guide the transition of single cells into a coherent bacterial community, by a proposed mechanism that is analogous to mitochondrial fusion and fission cycling that mixes contents to establish a homogenous population. In evolutionary terms, traA functions as a rare greenbeard gene that recognizes others that bear the same allele to confer beneficial treatment.

Author Summary

How individual cells recognize each other to cooperate and assemble functional tissues is a fundamental question in biology. Although multicellularity is a trait that is typically associated with eukaryotes, certain groups of bacteria also exhibit complex multicellular behaviors, which are perhaps best exemplified by the myxobacteria. For example, in response to starvation myxobacteria will assemble fruiting bodies, wherein thousands of cells function as a coherent unit in development and cell differentiation. However, how myxobacteria, or for that matter other bacteria, recognize cooperating partnering cells through cell contact-dependent interactions is poorly understood. Here we describe a mechanism where myxobacteria distinguish sibling and cohort cells from other myxobacteria isolates. We show that molecular recognition is mediated by a cell surface receptor called TraA. Cell-cell specificity involves mutual recognition by partnering cells and is mediated by proposed homotypic TraA interactions. The specificity for recognition is determined by variable sequences found within traA alleles. Thus, simply swapping traA alleles between isolates predictably changes partner recognition. TraA-TraA recognition in turn leads to the fusion and exchange of outer membrane (OM) components between cells. We suggest that OM exchange allows the cells to communicate and become homogenous with respect to their OM proteome. We further suggest these interactions build a cohesive cell population that functions in multicellular processes.