Antonie van Leeuwenhoek 81: 233–243, 2002. © 2002 Kluwer Academic Publishers. Printed in the Netherlands. 233 Cell to cell communication by autoinducing peptides in gram-positive bacteria Mark H.J. Sturme 1,* , Michiel Kleerebezem 2,3 , Jiro Nakayama 4 , Antoon D.L. Akkermans 1 , Elaine E. Vaughan 1,3 & Willem M. de Vos 1,3 1 Laboratory of Microbiology, Wageningen University, Hesselink van Suchtelenweg 4, 6703 CT, Wageningen, the Netherlands; 2 NIZO Food Research, Kernhemseweg 2, PO Box 20, 6710 BA Ede, the Netherlands; 3 Wageningen Centre for Food Sciences, Wageningen, the Netherlands; 4 Department of Bioscience and Biotechnology, Faculty of Agriculture, Kyushu University, 6-10-1 Hakozaki, Higashi-ku, Fukuoka 812-8581, Japan ( * Corresponding author: E-mail: mark.sturme@algemeen.micr.wau.nl) Key words: autoinducing peptides, Gram-positive bacteria, quorum sensing, two-component regulatory systems Abstract While intercellular communication systems in Gram-negative bacteria are often based on homoserine lactones as signalling molecules, it has been shown that autoinducing peptides are involved in intercellular communication in Gram-positive bacteria. Many of these peptides are exported by dedicated systems, posttranslationally modified in various ways, and finally sensed by other cells via membrane-located receptors that are part of two-component regulatory systems. In this way the expression of a variety of functions including virulence, genetic competence and the production of antimicrobial compounds can be modulated in a co-ordinated and cell density- and growth phase- dependent manner. Occasionally the autoinducing peptide has a dual function, such as in the case of nisin that is both a signalling pheromone involved in quorum sensing and an antimicrobial peptide. Moreover, biochemical, genetic and genomic studies have shown that bacteria may contain multiple quorum sensing systems, underlining the importance of intercellular communication. Finally, in some cases different peptides may be recognised by the same receptor, while also hybrid receptors have been constructed that respond to new peptides or show novel responses. This paper provides an overview of the characteristics of autoinducing peptide-based quorum sensing systems, their application in various gram-positive bacteria, and the discovery of new systems in natural and engineered ecosystems. Introduction It has been shown for several bacteria that a variety of physiological changes in the bacterial population are dependent on specific cell densities and growth phases. This phenomenon of cell density-dependent gene expression has been termed quorum sensing, and was first found in the control of biolumines- cence in Vibrio fischeri (Fuqua et al. 1994). Usually quorum sensing occurs at high cell densities, but in some cases also at relatively low densities, as was shown for genetic competence in Streptococcus pneu- moniae (Håvarstein et al. 1995b). Many other quorum sensing systems have been discovered since, in both Gram-negative and Gram-positive bacteria. Examples in Gram-negative bacteria include biofilm-formation and virulence in Pseudomonas aeroginosa (Winson et al. 1995; Singh et al. 2000), root-nodule formation by Rhizobium leguminosarum (Gray et al. 1996), and swarming motility of Serratia liquefaciens (Eberl et al. 1996). A comprehensive review on quorum sens- ing in Gram-negative bacteria is given in Whitehead et al. (2001). In Gram-positive bacteria quorum sensing regulation has been shown for: genetic competence in Bacillus subtilis (Tortosa & Dubnau 1999) and Strep- tococcus pneumoniae (Cheng et al. 1997), virulence in Staphylococcus aureus (Novick 1999), and the pro- duction of antimicrobial peptides, including bacteri- ocins and lantibiotics, in lactic acid bacteria (Kleere- bezem et al. 1997a; Risøen et al. 2000). In these quorum sensing systems bacteria produce extracellular signalling molecules that are responsible for the com-