PMID:23468628

Citation	Barrozo, RM, Cooke, CL, Hansen, LM, Lam, AM, Gaddy, JA, Johnson, EM, Cariaga, TA, Suarez, G, Peek, RM Jr, Cover, TL and Solnick, JV (2013) Functional plasticity in the type IV secretion system of Helicobacter pylori. PLoS Pathog. 9:e1003189
Abstract	Helicobacter pylori causes clinical disease primarily in those individuals infected with a strain that carries the cytotoxin associated gene pathogenicity island (cagPAI). The cagPAI encodes a type IV secretion system (T4SS) that injects the CagA oncoprotein into epithelial cells and is required for induction of the pro-inflammatory cytokine, interleukin-8 (IL-8). CagY is an essential component of the H. pylori T4SS that has an unusual sequence structure, in which an extraordinary number of direct DNA repeats is predicted to cause rearrangements that invariably yield in-frame insertions or deletions. Here we demonstrate in murine and non-human primate models that immune-driven host selection of rearrangements in CagY is sufficient to cause gain or loss of function in the H. pylori T4SS. We propose that CagY functions as a sort of molecular switch or perhaps a rheostat that alters the function of the T4SS and "tunes" the host inflammatory response so as to maximize persistent infection.
Links	PubMed PMC3585145 Online version:10.1371/journal.ppat.1003189
Keywords	Animals; Antigens, Bacterial/genetics; Antigens, Bacterial/immunology; Antigens, Bacterial/metabolism; Bacterial Proteins/genetics; Bacterial Proteins/immunology; Bacterial Proteins/metabolism; Bacterial Secretion Systems/physiology; DNA, Bacterial; Female; Helicobacter Infections/immunology; Helicobacter Infections/metabolism; Helicobacter Infections/microbiology; Helicobacter pylori/immunology; Helicobacter pylori/metabolism; Helicobacter pylori/ultrastructure; Host-Pathogen Interactions; Interleukin-8/metabolism; Macaca mulatta; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Microscopy, Electron, Scanning; Recombination, Genetic; Specific Pathogen-Free Organisms; Virulence Factors
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
HELPX:A7WPC5	involved_in	GO:0030255: protein secretion by the type IV secretion system	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete
HELPX:A7WPC5		GO:0030255: protein secretion by the type IV secretion system	ECO:0000315:		P		Figure 4 shows a deletion within the cagY allele significantly affects the ability to translocate proteins	complete CACAO 10097

References

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