A flowery toxin reveals its petals.

Now that physicians have grudgingly conceded that the bacterium Helicobacter pylori is responsible for most ulcers, and probably for some stomach cancer as well, the next step is to determine how it wreaks such havoc. In the spotlight is VacA an H. pylori molecule with proven toxicity to cells in testtube experiments. It causes large, fluid-filled spheres, called vacuoles, to appear in the cells.

While VacA's involvement in ulcers remains unclear, it does appear to be most active in acidic environments, which may help explain why H. pylori is destructive to the stomach. With the aid of a technique called deep-etch electron microscopy, developed by John E. Heuser of Washington University School of Medicine in St. Louis, investigators have recently analyzed the structure of VacA and its response to acid.

VacA normally assumes a flowerlike shape consisting of petals joined to a circular ring. In an acidic solution, however, the toxin breaks up into a dozen teardrop-shaped subunits, Timothy L. Cover of the Vanderbilt University School of Medicine in Nashville and his coworkers report in the Aug. 25 Journal of Cell Biology. According to their model of VacA, the toxin consists of two interlocked, six-petal rings. The researchers have not yet determined whether VacA's acid-induced toxicity results from the petals themselves or from their reassembly into some altered configuration.