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= Contact-Dependent Growth Inhibition (CDI) =

Contact-Dependent Growth Inhibition (CDI) is a phenomenon where a bacterial cell may deliver a polymorphic toxin molecule to its neighbouring cells upon direct cell-cell contact causing growth arrest or cell death.

History
CDI was first discovered in 2005 in an isolate of Echerichia coli found in rat intestine. The isolate was dominant in the gut flora and seen to be particularly good at outcompeting lab strains of E. coli. The inhibitory effects of the isolated E. coliI was seen to require direct cell-cell contact. A second system that could mediate CDI was discovered in 2006 in the pathogenic bacterium Vibrio cholerae, the cause of the gastro-intestinal disease cholera, and the opportunistic pathogen Pseudomonas aerugenosa. This CDI system was a whole new class of secretion systems which was named Type VI Secretion System.

CdiA
The CdiA system is encoded by the cdiBAI gene cluster which forms a two-partner Type V Secretion System for toxin delivery. cdiB encodes an outer membrane protein that exports and folds CdiA thus presenting it on the inhibitory cells' surface. The CdiA forms a conserved "stick-like" structure which can extend to be several nm long and interact with outer membrane receptors of neighbouring bacteria. The C-terminal of CdiA harbours a highly variable toxic domain which is delivered into the target bacterium upon receptor recognition thus inhibiting or killing the cell. cdiI encodes an immunity protein to prevent auto-inhibition by the C-terminal toxin. This also prevents the bacteria from killing or inhibiting the growth of their siblings as long as these possess the immunity gene.

Type IV Secretion System
The Type IV Secretion System (T4SS) is found in many species of Gram-negative and Gram-positive bacteria as well as in archea and are typically associated with conjugation or delivery of virulence proteins to eukaryotic cells. Some species of plant pathogen Xanthomonas, however, possess a particular T4SS capable of mediating CDI by delivering a peptidoglycan hydrolase. This effector kills targets that do not have the cognate immunity protein similar to other CDI systems.

Type VI Secretion System
The Type VI Secretion System (T6SS) is widely spread amongst Gram-negative bacteria and consists of a protein complex, encoded by several different genes, forming "needle-like" structure capable of injecting effector molecules into neighbouring target cells similar to the contractile tail of the T4 bacteriophage. One T6SS may have several different effectors such as PAAR-domain toxins or Hcp toxins and some species can deliver these toxins into both prokaryotes and eukaryotes.

Rhs Toxins
The Rearrangement hotspot system (Rhs) exists in both Gram-negative and Gram-positive bacteria. Similar to CdiA, these systems consists of big proteins with a conserved N-terminal domain and a variable C-terminal toxin domain requiring a cognate immunity protein. Many Rhs systems contain PAAR-domains (Proline-Alanine-Alanine-Arginine) which can interact with the VgrG of the T6SS apparatus making it required for Rhs secretion. The name Rearrangement hotspots comes from the discovery when the system was first identified as elements on the E. coli chromosome that were continuously rearranging. The Gram-positive soil bacterium Bacillus subtilis possesses an Rhs homolog called Wall-associated protein A (WapA) capable of mediating CDI whilst requiring a cognate immunity protein, WapI, to prevent auto-inhibition.

Cell Aggregation and Biofilm Formation
In E. coli the CdiA molecules may interact with those of other cells. This is believed to be cause cell-cell aggregation and promote biofilm formation. In a similar fashion, the CdiA homolog BcpA in Burkholderia thailandensis causes up regulation of genes encoding pili and polysaccharides when delivered to sibling cells which are in possession of the immunity protein BcpI. This change in gene expression leads to increased biofilm formation in the bacterial population through this Contact-Dependent Signalling. Furthermore, the T6SS in V. cholerae is active in biofilms to killi nearby cells which do not have the specific immunity.