Toxic component of a toxin-immunity protein module, which functions as a cellular contact-dependent growth inhibition (CDI) system. CDI modules allow bacteria to communicate with and inhibit the growth of closely related neighboring bacteria (target cell counts decrease 1000- to 10(5)-fold) in a contact-dependent fashion. Inhibitory cells must be in logarithmic (not stationary) phase to inhibit growth of their targets, but protein synthesis is not necessary. The presence of P or S but not type 1 pili protects the target cells against growth inhibition for this CDI. BamA on the outer membrane of target cells acts as a receptor for CdiA, while target cell multidrug efflux pump AcrB facilitates its transport into the cytoplasm. Outer membrane receptor function is dependent on extracellular loops of BamA. Cells undergoing CDI show a 2- to 5-fold reversible decrease in aerobic respiration, proton motive force and steady-state ATP levels, suggesting this CT module is an ionophore that disrupts the target cell's inner cell membrane. Growth recovery requires an energy source. Cells expressing this protein in the absence of CdiI initially form filaments, some of which contain multiple nucleoids, while others are devoid of nucleoids. CDI cells induce the phage shock response, but pspA is not required for recovery from CDI. CDI is neutralized by its cognate immunity protein CdiI, but not by non-cognate CdiI from other bacteria with different CDI systems. Plays a role in biofilm formation, a region N-terminal to residue 644 is implicated in this receptor-independent cell adhesion (Ref.6).; The CdiA protein is thought to be exported from the cell through the central lumen of CdiB, the other half of its two-partner system (TPS). The TPS domain probably remains associated with CdiB while the FHA-1 domain forms an extended filament (33 nm long) with the receptor-binding domain (RBD) at its extremity; in the secretion arrested state the C-terminus of the RBD and YP domains form a hairpin-like structure as the FHA-2, PT and CT domains are periplasmic. The YP domain is probably responsible for this arrest at the point where it re-enters the host cell periplasm. Upon binding to a target cell outer membrane receptor (BamA for this CDI) a signal is transmitted to activate secretion. The filament becomes about 5 nm longer, the rest of CdiA is secreted and the FHA-2 domain becomes stably associated with the target cell's outer membrane where it facilitates entry of the toxic CT domain into the target cell periplasm. From there the toxic CT domain is cleaved and gains access to the target cell cytoplasm via an inner membrane protein (multidrug efflux pump AcrB for this CDI).
