Mechanisms and Biological Roles of Contact-Dependent Growth Inhibition Systems

Bacterialcontact-dependentgrowthinhibition(CDI)ismediatedbytheCdiA/CdiBfamilyof two-partner secretion proteins. CDI þ cells bind to susceptible target bacteria and deliver a toxic effector domain derived from the carboxyl terminus of CdiA (CdiA-CT). More than 60 distinct CdiA-CT sequence types have been identified, and all CDI toxins characterized thus far display RNase, DNase, or pore-forming activities. CDI systems also encode CdiI immunity proteins, which specifically bind and inactivate cognate CdiA-CT toxins to prevent autoinhibition. CDI activity appears to be limited to target cells of the same species, suggestingthatthesesystemsplayaroleincompetitionbetweencloselyrelatedbacteria.Recent workontheCDIsystemfromuropathogenicEscherichiacoli (UPEC536)hasrevealedthatits CdiA-CT toxin binds tightly to a cysteine biosynthetic enzyme (CysK) in the cytoplasm of targetcells.TheunanticipatedcomplexityintheUPECCDIpathwayraisesthepossibilitythat these systems perform other functions in addition to growth inhibition. Finally, we propose that the phenomenon of CDI is more widespread than previously appreciated. Rhs (rearrangement hotspot) systems encode toxin-immunity pairs, some of whichshare significant sequence identity with CdiA-CT/CdiI proteins. A numberof recent observations suggest that Rhs proteins mediate a distinct form of CDI.