The Helicobacter pylori CagA Protein: A Multifunctional Bacterial Toxin Delivered by Type IV Secretion
Wolfgang Fischer and Benjamin Busch
from: Bacterial Toxins: Genetics, Cellular Biology and Practical Applications (Edited by: Thomas Proft). Caister Academic Press, U.K. (2013)
Abstract
To deliver proteins with host cell-modulating activities, pathogenic bacteria either secrete protein toxins that are able to enter target cells autonomously, or use specialized secretion systems (type III, type IV or type VI secretion systems) to inject effector proteins directly into the host cell cytosol. The human gastric pathogen Helicobacter pylori secretes one major virulence determinant, the vacuolating cytotoxin VacA, to the extracellular environment, and translocates another, the cytotoxin-associated antigen CagA, by contact-dependent injection using the Cag type IV secretion system. Transfer of CagA into host cells is considered as a major risk factor for development of gastric cancer, and ectopically expressed CagA is sufficient to cause neoplastic transformations. Once injected, CagA becomes phosphorylated by cellular tyrosine kinases, and the subsequent interaction with a large number of host cell proteins results in cytoskeleton rearrangements and in deregulation of several signal transduction pathways that may lead to precancerous changes. Moreover, CagA binds to several interaction partners independently of tyrosine phosphorylation, and these interactions lead to a loss of cell polarity and to increased cell motility. This review summarizes the current knowledge of the molecular mechanisms of the CagA translocation process and of the diverse functions of CagA in target cells read more ...
