G. Bukholm et al., COLONY VARIATION OF HELICOBACTER-PYLORI - PATHOGENIC POTENTIAL IS CORRELATED TO CELL-WALL LIPID-COMPOSITION, Scandinavian journal of gastroenterology, 32(5), 1997, pp. 445-454
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.