The dominant lineage of an emerging pathogen harbours contact-dependent inhibition systems.

Bacteria from the complex (Smc) are important multidrug-resistant pathogens that cause a broad range of infections. Smc is genomically diverse and has been classified into 23 lineages. Lineage Sm6 is the most common among sequenced strains, but it is unclear why this lineage has evolved to be dominant. Antagonistic interactions can significantly affect the evolution of bacterial populations. These interactions may be mediated by secreted contact-dependent proteins, which allow inhibitor cells to intoxicate adjacent target bacteria. Contact-dependent inhibition (CDI) requires three proteins: CdiA, CdiB and CdiI. CdiA is a large, filamentous protein exported to the surface of inhibitor cells through the pore-like CdiB. The CdiA C-terminal domain (CdiA-CT) is toxic when delivered into target cells of the same species or genus. CdiI immunity proteins neutralize the toxicity of cognate CdiA-CT toxins. We found that all complete Smc genomes from the Sm6 lineage harbour at least one CDI locus. By contrast, less than a quarter of strains from other lineages have CDI genes. Smc CdiA-CT domains are diverse and have a broad range of predicted functions. Most Sm6 strains harbour non-cognate genes predicted to provide protection against foreign toxins from other strains. Finally, we demonstrated that an Smc CdiA-CT toxin has antibacterial properties and is neutralized by its cognate CdiI.