CagA: a role at last

Comment†

Many strains of Helicobacter pyloriproduce an immunogenic high molecular weight protein called cytotoxin associated gene product A (CagA) and infection with such strains can be detected by a simple serological test for anti-CagA antibodies. Numerous studies over the past nine years have shown that CagA positive infections are more likely than CagA negative infections to result in gastroduodenal ulceration or gastric carcinoma. Despite this, to date no direct role for CagA in pathogenesis or function has been found. Now, four independent groups have shown that CagA is delivered byH pylori into gastric epithelial cells where it is phosphorylated, and triggers profound changes in the host cytoskeleton.1-4 This should help explain the enhanced virulence of CagA positive H pyloristrains.

Previously, H pylori has been shown to induce changes in gastric epithelial cells during attachment.5 The microvilli disappear at the site of attachment, the cytoskeleton is rearranged beneath the bacterium, and a cup shaped pedestal forms beneath the bacterium. At the same time, intracellular signalling changes can be detected inside the epithelial cell with phosphorylation of proteins on tyrosine residues—a classic cellular signalling pathway. The major phosphorylated protein has now been shown not to be a host cell protein, but H pylori CagA.1-4 The four groups involved have shown this conclusively using a variety of methods: the phosphorylated protein varies in size according to the size of CagA in theH pylori strain and is not induced by CagA negative mutants; it is ³⁵S labelled if the bacterium is so labelled before …