In Helicobacter pylori , LuxS Is a Key Enzyme in Cysteine Provision through a Reverse Transsulfuration Pathway

Abstract

ABSTRACT 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 Δ luxS Hp mutant was restored by homocysteine or cystathionine and growth of the Δ cysK Hp mutant by cystathionine only. The Δ metB Hp mutant had an absolute requirement for cysteine. Metabolite analyses showed that S -ribosylhomocysteine accumulated in the Δ luxS Hp mutant, homocysteine in the Δ cysK Hp mutant, and cystathionine in the Δ metB 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.