CdiA promotes receptor-independent intercellular adhesion

Abstract

CdiB/CdiA proteins mediate inter-bacterial competition in a process termed contact-dependent growth inhibition (CDI). Filamentous CdiA exoproteins extend from CDI+ cells and bind specific receptors to deliver toxins into susceptible target bacteria. CDI has also been implicated in auto-aggregation and biofilm formation in several species, but the contribution of CdiA-receptor interactions to these multi-cellular behaviors has not been examined. Using Escherichia coli isolate EC93 as a model, we show that cdiA and bamA receptor mutants are defective in biofilm formation, suggesting a prominent role for CdiA-BamA mediated cell-cell adhesion. However, CdiA also promotes auto-aggregation in a BamA-independent manner, indicating that the exoprotein possesses an additional adhesin activity. Cells must express CdiA in order to participate in BamA-independent aggregates, suggesting that adhesion could be mediated by homotypic CdiA-CdiA interactions. The BamA-dependent and BamA-independent interaction domains map to distinct regions within the CdiA filament. Thus, CdiA orchestrates a collective behavior that is independent of its growth-inhibition activity. This adhesion should enable 'greenbeard' discrimination, in which genetically unrelated individuals cooperate with one another based on a single shared trait. This kind-selective social behavior could provide immediate fitness benefits to bacteria that acquire the systems through horizontal gene transfer. CdiB/CdiA two-partner secretion systems mediate inter-bacterial competition in a process termed contact-dependent growth inhibition (CDI). CDI+ cells use CdiA proteins to bind specific receptors on target bacteria and deliver inhibitory toxins. Here, we show that CdiA from E. coli EC93 also mediates receptor-independent cell-cell adhesion through a putative homotypic interaction domain. CdiA-CdiA binding interactions promote auto-aggregation and biofilm formation, demonstrating a role in collective behavior that is independent of growth-inhibition activity.