Abstract
BackgroundHelicobacter pylori specifically takes up cholesterol and incorporates it into the bacterial membrane, yet little is currently known about cholesterol's physiological roles. We compared phenotypes and in vivo colonization ability of H. pylori grown in a defined, serum-free growth medium, F12 with 1 mg/ml albumin containing 0 to 50 μg/ml cholesterol.ResultsWhile doubling times were largely unaffected by cholesterol, other overt phenotypic changes were observed. H. pylori strain SS1 grown in defined medium with cholesterol successfully colonized the stomach of gerbils, whereas SS1 grown without cholesterol failed to colonize. H. pylori lipopolysaccharide often displays Lewis X and/or Y antigens. Expression of these antigens measured by whole-cell ELISA was markedly enhanced in response to growth of strain SS1, 26695, or G27 in cholesterol. In addition, electrophoretic analysis of lipopolysaccharide in wild type G27 and in mutants lacking the O-chain revealed structural changes within the oligosaccharide core/lipid A moieties. These responses in Lewis antigen levels and in lipopolysaccharide profiles to cholesterol availability were highly specific, because no changes took place when cholesterol was substituted by β-sitosterol or bile salts. Disruption of the genes encoding cholesterol α-glucosyltransferase or lipid A phosphoethanolamine transferase had no effect on Lewis expression, nor on lipopolysaccharide profiles, nor on the cholesterol responsiveness of these properties. Disruption of the lipid A 1-phosphatase gene eliminated the effect of cholesterol on lipopolysaccharide profiles but not its effect on Lewis expression.ConclusionsTogether these results suggest that cholesterol depletion leads to aberrant forms of LPS that are dependent upon dephosphorylation of lipid A at the 1-position. A tentative model for the observed effects of cholesterol is discussed in which sequential steps of lipopolysaccharide biogenesis and, independently, presentation of Lewis antigen at the cell surface, depend upon membrane composition. These new findings demonstrate that cholesterol availability permits H. pylori to modify its cell envelope in ways that can impact colonization of host tissue in vivo.
Highlights
Helicobacter pylori takes up cholesterol and incorporates it into the bacterial membrane, yet little is currently known about cholesterol's physiological roles
Gerbils were colonized only by the cultures grown in cholesterol-containing medium, but not by H. pylori grown in cholesterol-free medium (In each experiment, P < .0001 for comparison of log (CFU/g) between groups using Student two-tailed t-test)
Taking into account that H. pylori can acquire cholesterol from the membrane of host gastric epithelial cells [35], our data would suggest that incorporation of cholesterol into the bacterial membrane prior to inoculation may facilitate early steps in gastric colonization that precede adherence to host epithelium, such as motility and/
Summary
Helicobacter pylori takes up cholesterol and incorporates it into the bacterial membrane, yet little is currently known about cholesterol's physiological roles. BMC Microbiology 2009, 9:258 http://www.biomedcentral.com/1471-2180/9/258 bacterium must survive transit through the acidic gastric compartment [1] It penetrates and establishes residence in the protective mucus layer, a lipid- and cholesterol-rich environment [2,3]. H. pylori Lewis antigens have been linked to the severity of peptic ulcer and duodenitis [16,22] Another important feature of H. pylori LPS is its modified lipid A structure, with reduced acylation and fewer charged groups than is typical of enterobacteria [23]. These lipid A modifications minimize endotoxic and inflammatory properties of H. pylori LPS (reviewed in [24])
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