THE HUMAN GASTRIC PATHOGEN HELICOBACTER-PYLORI HAS A GENE ENCODING ANENZYME FIRST CLASSIFIED AS A MUCINASE IN VIBRIO-CHOLERAE

The human bacterial pathogen Helicobacter pylori has been suggested to be the causative agent of the most common chronic infection of man. S ince its first isolation in 1982, H. pylori has been associated with g astric and duodenal ulcer disease, and more recently, gastric cancer. The proteolytic digestion of gastric mucus by this microorganism has b een suggested as an important mechanism by which its pathogenicity is at least partly exerted. Here we report the detection of protease acti vity in H. pylori total-cell and supernatant extracts. On the basis th at zinc metalloproteases are common microbial pathogenicity factors, w e identified a single protein in H. pylori protein extracts with antib odies to the Pseudomonas aeruginosa elastase (a secreted zinc metallop rotease). This same protein was identified by pooled serum from patien ts infected with H. pylori. We used the functional and immunological r elationship between the P. aeruginosa elastase and the Vibrio cholerae haemagglutinin/protease (HAP) to clone the H. pylori hap gene, which was over 99% similar to the V. cholerae hap gene in the coding region. A 4 kb DNA fragment containing the entire cloned gene was highly unst able in Escherichia coli and Bacillus subtilis cloning vectors. We als o demonstrated that a hap-like gene sequence is present in all nine He licobacter species so far discovered. The V. cholerae HAP was first cl assified on the basis of its mucinase activity.