CdiA promotes receptor‐independent intercellular adhesion

Summary 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.