Mechanisms and biological roles of contact-dependent growth inhibition systems.
Bacterial contact-dependent growth inhibition (CDI) is mediated by the CdiA/CdiB family of two-partner secretion proteins. CDI(+) 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, suggesting that these systems play a role in competition between closely related bacteria. Recent work on the CDI system from uropathogenic Escherichia coli (UPEC 536) has revealed that its CdiA-CT toxin binds tightly to a cysteine biosynthetic enzyme (CysK) in the cytoplasm of target cells. The unanticipated complexity in the UPEC CDI pathway raises the possibility that 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 which share significant sequence identity with CdiA-CT/CdiI proteins. A number of recent observations suggest that Rhs proteins mediate a distinct form of CDI.
Department of Molecular, Cellular and Developmental Biology, University of California, Santa Barbara, Santa Barbara, California 93106-9625.
Christopher S
CS
Hayes
Sanna
S
Koskiniemi
Zachary C
ZC
Ruhe
Stephen J
SJ
Poole
David A
DA
Low
D001422:Bacterial Adhesion / Q000502:physiology*; D001425:Bacterial Outer Membrane Proteins / Q000502:physiology; D001427:Bacterial Toxins / Q000378:metabolism; D019117:Burkholderia / Q000502:physiology; D003260:Contact Inhibition / Q000502:physiology*; D004926:Escherichia coli / Q000502:physiology; D029968:Escherichia coli Proteins / Q000378:metabolism / Q000502:physiology*; D008565:Membrane Proteins / Q000378:metabolism / Q000502:physiology*
D001425:Bacterial Outer Membrane Proteins; D001427:Bacterial Toxins; C503242:CdiA protein, E coli; D029968:Escherichia coli Proteins; D008565:Membrane Proteins