In Helicobacter pylori, LuxS is a key enzyme in cysteine provision through a reverse transsulfuration pathway.

In many bacteria, LuxS functions as a quorum-sensing molecule synthase. However, it also has a second, more central metabolic function in the activated methyl cycle (AMC), which generates the S-adenosylmethionine required by methyltransferases and recycles the product via methionine. Helicobacter pylori lacks an enzyme catalyzing homocysteine-to-methionine conversion, rendering the AMC incomplete and thus making any metabolic role of H. pylori LuxS (LuxS(Hp)) unclear. Interestingly, luxS(Hp) is located next to genes annotated as cysK(Hp) and metB(Hp), involved in other bacteria in cysteine and methionine metabolism. We showed that isogenic strains carrying mutations in luxS(Hp), cysK(Hp), and metB(Hp) could not grow without added cysteine (whereas the wild type could), suggesting roles in cysteine synthesis. Growth of the DeltaluxS(Hp) mutant was restored by homocysteine or cystathionine and growth of the DeltacysK(Hp) mutant by cystathionine only. The DeltametB(Hp) mutant had an absolute requirement for cysteine. Metabolite analyses showed that S-ribosylhomocysteine accumulated in the DeltaluxS(Hp) mutant, homocysteine in the DeltacysK(Hp) mutant, and cystathionine in the DeltametB(Hp) mutant. This suggests that S-ribosylhomocysteine is converted by LuxS(Hp) to homocysteine (as in the classic AMC) and thence by CysK(Hp) to cystathionine and by MetB(Hp) to cysteine. In silico analysis suggested that cysK-metB-luxS were acquired by H. pylori from a Gram-positive source. We conclude that cysK-metB-luxS encode the capacity to generate cysteine from products of the incomplete AMC of H. pylori in a process of reverse transsulfuration. We recommend that the misnamed genes cysK(Hp) and metB(Hp) be renamed mccA (methionine-to-cysteine-conversion gene A) and mccB, respectively.

The effect of the human gut-signalling hormone, norepinephrine, on the growth of the gastric pathogen Helicobacter pylori.

BACKGROUND AND AIMS: Helicobacter pylori is an important human pathogen, infecting around half the population of the world. It has developed a number of refinements to allow it to persist in the human stomach. Catecholamine hormones have been shown to enhance growth of other bacterial species and are found in the gastric niche. We aimed to study growth enhancement of H. pylori by the human catecholamine hormones epinephrine and norepinephrine. METHODS: Growth studies were carried out in complex and defined media containing the hormones epinephrine, norepinephrine, and normetanephrine, the main host metabolite of norepinephrine. Bacterial density was measured by viable count or optical density. Intracellular ATP was measured using a bioluminescence assay technique. RESULTS: Both epinephrine and norepinephrine enhanced H. pylori growth in a dose-dependent strain-independent fashion, with norepinephrine being more effective than epinephrine. We showed a rapid (4 hours) dose-dependent effect on metabolic activity, as measured by intracellular ATP levels. We used a chemically defined medium to study mechanisms: chelation of ferric iron blocked H. pylori growth, which could be overcome by addition of norepinephrine. Disruption of the catechol group of norepinephrine abrogated its H. pylori-growth-promoting activity. CONCLUSIONS: Norepinephrine stimulates growth of H. pylori under otherwise growth-restricted conditions, and this effect is related to the ability of norepinephrine to bind ferric iron. This supports the notion that norepinephrine may aid H. pylori persistence in the stomach.