COLONY VARIATION OF HELICOBACTER-PYLORI - PATHOGENIC POTENTIAL IS CORRELATED TO CELL-WALL LIPID-COMPOSITION

Background: Differences in expression of disease after infection with Heiicobacter pylori have so far been connected with host factors and b acterial interstrain variation. In this study, spontaneous and ecology -mediated intrastrain variation was examined. Methods: Four clinical i solates of H. pylori were shown to give rise to two colony forms. Bact erial morphology was examined by electron microscopy. Bacterial fracti ons were examined for proteins using ion exchange chromatography and S DS-PAGE; for lipids using thin-layer chromatography, lipid anion-excha nge chromatography, column chromatography on silica gel, P-31-NMR, gas chromatography and mass spectrometry. Bacterial in vitro invasiveness and adhesiveness were examined in two different systems, and urease a nd VacA toxin were assayed by Western blot analysis. Results: H. pylor i was shown to give rise to two colony forms: at normal pH the populat ion was dominated by L colonies. One strain was chosen for further stu dies. Bacteria from L colonies retained VacA toxin and urease, did not invade or adhere to epithelial cells, and contained normal quantities of phosphatidylethanolamine. In a small frequency, spontaneous S colo nies were formed. Bacteria from these colonies released VacA and ureas e, adhered to and invaded epithelial cells and contained increased amo unts of lysophosphatidyl ethanolamine and phosphatidyl serine. After a ddition of HCl to the culture medium (pH 6), almost only S colonies we re formed. The results demonstrate that environmental factors, such as HCl, can change the bacterial cell wall, and thereby enhance expressi on of virulence factors of H. pylori in vitro. A similar in vivo varia tion would have implications for our understanding of the interaction between HCl secretion in the gastric mucosa and H. pylori in the devel opment of peptic ulcer disease.