The LuxS family of bacterial autoinducers: biosynthesis of a novel quorum-sensing signal molecule

Many bacteria control gene expression in response to cell population densit y, and this phenomenon is called quorum sensing. In Gram-negative bacteria, quorum sensing typically involves the production, release and detection of acylated homoserine lactone signalling molecules called autoinducers. Vibr io harveyi, a Gram-negative bioluminescent marine bacterium, regulates ligh t production in response to two distinct autoinducers (AI-1 and AI-2). AI-1 is a homoserine lactone. The structure of AI-2 is not known. We have sugge sted previously that V. harveyi uses AI-1 for intraspecies communication an d AI-2 for interspecies communication. Consistent with this idea, we have s hown that many species of Gramnegative and Gram-positive bacteria produce A I-2 and, in every case, production of AI-2 is dependent on the function enc oded by the luxS gene. We show here that LuxS is the AI-2 synthase and that AI-2 is produced from S-adenosylmethionine in three enzymatic steps. The s ubstrate for LuxS is S-ribosylhomocysteine, which is cleaved to form two pr oducts, one of which is homocysteine, and the other is AI-2. In this report , we also provide evidence that the biosynthetic pathway and biochemical in termediates in AI-2 biosynthesis are identical in Escherichia coli, Salmone lla typhimurium, V. harveyi, Vibrio cholerae and Enterococcus faecalis. Thi s result suggests that, unlike quorum sensing via the family of related hom oserine lactone autoinducers, AI-2 is a unique, 'universal' signal that cou ld be used by a variety of bacteria for communication among and between spe cies.