Toxin on a stick

Contact-dependent growth inhibition (CDI) is the first contact-dependent competition system identified in bacteria. CDI is mediated by the CdiA/CdiB two-partner secretion system, and the BamA outer membrane protein serves as the CDI receptor on target cells. A small immunity protein, CdiI, is required to protect inhibitor cells from their own CDI system. Recent results from our group show that CDI systems are present in a number of important gram-negative plant and animal pathogens. The C-terminal region of CdiA (CdiA-CT) is polymorphic and contains growth inhibitory activity. The CdiA-CT from uropathogenic Esherichia coli 536 is a tRNase whereas a CdiA-CT from Dickeya dadantii 3937 has DNase activity. Accordingly, these bacteria contain distinct CdiI proteins, which specifically bind and inactivate cognate CdiA-CT. Remarkably, CdiA-CTs are modular: one CdiA "stick" can deliver different CdiA-CT toxins. We discuss these findings as well as results showing that CDI plays an important role in intra-strain bacterial competition in the natural world. A detailed mechanistic understanding of CDI could facilitate development of probiotics and antimicrobials that target specific pathogens.