Class II contact-dependent growth inhibition (CDI) systems allow for broad-range cross-species toxin delivery

Contact-dependent growth inhibition (CDI) allows bacteria to recognize kin cells in mixed bacterial populations. In Escherichia coli, CDI mediated effector delivery has been shown to be species-specific, with a preference for the own strain over others. This specificity is achieved through an interaction between a receptor-binding domain in the CdiA protein and its cognate receptor protein on the target cell. But how conserved this specificity is has not previously been investigated in detail. Here we show that three different class II CdiA receptor-binding domains and their Enterobacter cloacae analog are highly promiscuous, allowing for efficient effector delivery into several different Enterobacteriaceae species, including Escherichia, Enterobacter, Klebsiella and Salmonella spp. In addition, although we observe a preference for some receptors over others, this did not limit cross-species effector delivery, suggesting that class II CdiA proteins can allow for broad-range and cross-species growth inhibition in mixed bacterial populations.