Detoxification of 7-Dehydrocholesterol Fatal to Helicobacter pylori Is a Novel Role of Cholesterol Glucosylation

Abstract

The glucosylation of free cholesterol (FC) by Helicobacter pylori cells has various biological significances for the survival of this bacterium. H. pylori cells with glucosylated FC are capable of evading host immune systems, such as phagocytosis by macrophages and activation of antigen-specific T cells, and surviving in the gastric mucosal tissues for long periods. An additional role of cholesterol glucosylation in the survival of H. pylori which is distinct from the role of escaping the host immune system, however, has yet to be identified. This study demonstrated that 7-dehydrocholesterol (7dFC), an FC precursor, is a toxic compound fatal to H. pylori cells, but the cell membrane of H. pylori is capable of absorbing this toxic sterol via glucosylation. In contrast to the case with 7dFC, no toxicity to H. pylori cells was detected from the glucosylated 7dFC. In addition, cgt gene mutant H. pylori cells that cannot glucosylate cholesterols had higher susceptibility to the toxic action of 7dFC than wild-type H. pylori cells. These results indicate that the cgt gene product of H. pylori serves to detoxify the sterol fatal to this bacterium and to permit this toxic sterol as a cell membrane lipid component. In summary, this study defined a novel role of cholesterol glucosylation in H. pylori.

Cholesterol lipids and cholesterol-containing lipid rafts in bacteria

“…However, the effect of the cholesterol biosynthetic precursor 7-dehydrocholesterol (7DHC) has been studied. It was found to be fatal to H. pylori (49). Glucosylation detoxified 7DHC, as indicated by the observation that mutant H. pylori lacking the ability to glucosylate cholesterol had higher 7DHC susceptibility (49).…”

“…It was found to be fatal to H. pylori (49). Glucosylation detoxified 7DHC, as indicated by the observation that mutant H. pylori lacking the ability to glucosylate cholesterol had higher 7DHC susceptibility (49). The effect of other steroids upon H. pylori has also been studied.…”

Synthesis and Structural Characterization of Three Unique Helicobacter pylori α‐Cholesteryl Phosphatidyl Glucosides

“…Likewise, we have demonstrated that the phosphoramidite chemistry is compatible with biologically relevant functional groups such as olefins and cyclopropanes. In light of the recent discovery that H. pylori enzymes are promiscuous and readily incorporate a variety of cholesterol analogues,16 this modular platform offers accessibility to various phosphatidyl glycolipids to study their biological properties and also to aid in the discovery of new analogues.…”

Hijacking and Use of Host Lipids by Intracellular Pathogens

“…The glucosyl-cholesterol complex can be beneficial to H. pylori , because this bacterium can glucosylate toxic sterols and integrate the complex into the membrane without harming the organism. In contrast, mutants of the glucosyl transferase are killed by toxic sterols (159). Cholesterol in H. pylori modifies the membranes so that colonization of the gastric mucosa and expression of Lewis antigen are not impaired (160).…”