Title: Quorum sensing and probiotics
Key words: quorum sensing, probiotics, bacteria, autoinducers, lactobacilli, peptides, A1-2 class, bacteriocins, bacteriocidal, autoregulation, pH, temperature, medium composition, genomic studies, lactic acid producers, stomach, viability, gene structure
Date: Sept 2006
Category: The Gut
Author: Morgan, G
Quorum sensing and probiotics
Quorum sensing is a strategy of intercellular communication within a unicellular population enabling the regulation of its genetic and metabolic function in response to cellular density. In effect it allows a bacterial population to function as a coordinated multicellular organism to the benefit of the population as a whole. Its role as a universal control system within bacterial populations has now been well described (Dunny 1997). The understanding of the mechanisms of such systems is important in furthering research into probiotics and will be commented upon here.
In all bacterial populations studied, quorum sensing has been found to be effected through a group of hormone or pheromone-like molecules called autoinducers (AIs). In the case of lactobacilli, the gram-positive class of probiotics that have been most extensively studied, these are either peptides or an as yet non-categorised class of compounds (the so-called AI-2 class). The prevalence of AI-2s amongst a broad range of bacterial species has been well documented (Sperandio 2001). One single AI-2 associated gene, the luxS, for example, has been linked to the co-expression of at least 10% of the genome in one strain of E. Coli : it is present amongst a wide range of bacterial species and has been shown to exert significant metabolic, growth, toxic and bacteriocidal effects (Surette 1998, Surette 1999, Sperandio 2001). Similar effects in lactobacilli have been documented with other AIs (Kuipers 1995, Diep 2001, Eijsink 2002).
The specificity of autoinducers has been well demonstrated in the case of bacteriocins in lactobacilli (Eijsink 2002). Bacteriocins have a narrow range of activity and may be bacteriocidal to strains even within the same species. Nisin, the most studied lactobacillus bacteriocidin (Kuipers 1995, Quadri 2002), in fact acts as its own autoinducer. Other bacteriocins are linked to dedicated AIs, some of which have structural similarities with their cognate bacteriocins, and, indeed, may possess some bactericidal activity in their own right (Kuipers 1995). The genes involved in such systems are arranged in clusters, AI expression being closely linked with adjacent histidine phosphokinase and response regulating genes (West 2001).
Activation of such complexes leads to the autoregulation of a series of genes regulating bacteriocin production, growth and metabolic function. Associated gene promotion has been demonstrated in a number of species and has been found to be determined by quorum sensing responses to changes in medium composition, intracellular metabolites, pH, temperature, oxygen availability and other factors (Baca-deLancy 1999, Brurberg 1997, Diep 2000, Nilsen 1998). Nisin and its autoinduction function has been associated with initial promotion of cell division and later with growth inhibition (Kuipers 1995).The close association between autoinducer and bacteriocin structure and function in the case of nisin has been demonstrated in experimental manipulation of the nisin gene, variants being associated with a loss of AI activity but a gain of bactericidal activity (Quadri 2002).
Genomic studies are now helping to unravel the structural complexities of systems such as lactobacilli gene clusters. Autoinducer, bacteriocin, immunity protein and transport genes form closely associated structures that are involved in the assembly of a range of proteins that are type specific. The bacteriocins produced enable the strain involved to expand its terrain whilst being protected by its own immunity proteins. Quorum sensing, acting through autoinducers, enables this to occur through monitoring of the external environment and by adjustments to the internal milieu.
Given the present level of understanding and the technical improvements within the field of genetic engineering, the development of increasingly effective probiotics is now a realistic target. Viability and effectiveness are problems which have dogged probiotic research for many years. Though lactic acid producers are able to survive in a highly specialised environment, probiotics are frequently unable to survive the journey through the stomach into the small intestine and there to become adherent to the mucosa and to proliferate. Strains with increased viability, adherence and prolixity (Goulet 2003) need to be developed in order to harvest the full potential of these bacteria with their associated health benefits. Strains which may be beneficial in treating specific medical disorders will also need to be developed. An understanding of gene structure and function and of quorum sensing will thus be vital in order to help realise these objectives.
1. Dunny GM, Leonard BA (1997) Cell-cell communication in gram- positive bacteria. Annu Rev Microbiol 51: 527-564
2. Sperandio V, Torres AG, Giron JA, Kaper JB (2001) Quorum sensing is a global regulatory mechanism in enterohemorrhagic Escherichia coli 0157:H7. J Bacteriol 183: 5187-97
3. Surette MG, Bassler BL (1998) Quorum sensing in Escherichia coli, and Salmonella typhimurium. Proc Natl Acad Sci USA 95: 15196-15201
4. Surette MG,Miller MB, Bassler BL (1999) Quorum sensing in Echerichia coli, Salmonella typhimurium and Vibrio harveyi: a new family of genes responsible for autoinducer production. Proc Natl Acad Sci USA 96: 1639-44
5. Kuipers OP, Beerthuyzen Mm, De Ruyter PG, Luesink EJ, De Vos WM (1995) Autoregulation of nisin biosynthesis in Lactococcus lactis by signal transduction. J Biol Chem 270:27299-27304
6. Diep DB, Johnsborg O, Risoen PA, Nes IF (2001) Evidence for dual functionality of the operon plnABCD in the regulation of bacteriocin production in Lactobacillus plantarum. Mol Microbiol 41: 633-644
7. Eijsink VGH, et al. (2002) Production of class II bacteriocins by lactic acid bacteria; an example of biological warfare and communication. Antonie van Leeuwenhoek 81: 639-654
8. Quadri LEN (2002) Regulation of antimicrobial peptide production by autoinducer-mediated quorum sensing in lactic acid bacteria. Antonie van Leeuwenhoek 82: 133-145
9. West AH, Stock AM (2001) Histidine kinases and response regulator proteins in two-component signalling systems. Trends Biochem Sci 26: 369-76
10. Baca-deLancey RR, South MM, Ding X, Rather
PN (1999) Escherichia coli genes regulated by cell-to-cell signalling. Proc Natl Acad Sci
11. Brurberg MB, Nes IF, Eijsink VGH (1997) Pheromone-induced production of antimicrobial peptides in Lactobacillus. Mol Microbiol 26: 347-60
12. Diep DB, Axelsson L, Grefsli C, Nes IF (2000) The synthesis of the bacteriocin sakacin A is a temperature-sensitive process regulated by a pheromone peptide through a three-component regulatory system. Microbiology 146: 2155-2160
13. Nilsen T, Nes IF, Holo H (1998) An exported inducer peptide regulates bacteriocin production in Enterococcus faecium CTC492. J Bacteriol 180: 1848-54
14. Goulet J (2003) Lecture notes. Surrey University