What is Quorum sensing and how do bacteria talk to each other?

1. What is Quorum sensing and how do bacteria talk to each other? The discovery that bacteria are able to communicate with each other changed our general perception of many single, simple organisms inhabiting our world. Instead of language, bacteria use signalling molecules which are released into the environment. As well as releasing the signalling molecules, bacteria are also able to measure the number (concentration) of the molecules within a population. Nowadays we use the term 'Quorum Sensing' (QS) to describe the phenomenon whereby the accumulation of signalling molecules enable a single cell to sense the number of bacteria (cell density). In the natural environment, there are many different bacteria living together which use various classes of signalling molecules. As they employ different languages they cannot necessarily talk to all other bacteria. Today, several quorum sensing systems are intensively studied in various organisms such as marine bacteria and several pathogenic bacteria.

2. Why do bacteria talk to each other? QS enables bacteria to co-ordinate their behaviour. As environmental conditions often change rapidly, bacteria need to respond quickly in order to survive. These responses include adaptation to availability of nutrients, defence against other microorganisms which may compete for the same nutrients and the avoidance of toxic compounds potentially dangerous for the bacteria. It is very important for pathogenic bacteria during infection of a host (e.g. humans, other animals or plants) to co-ordinate their virulence in order to escape the immune response of the host in order to be able to establish a successful infection.

4. Do all bacteria use the same signal molecules? Different bacterial species use different molecules to communicate. There are several different classes of signalling molecule (see examples). Within each class there are also minor variations such as length of side chains etc. In some cases a single bacterial species can have more than one QS system and therefore use more than one signal molecule. The bacterium may respond to each molecule in a different way. In this sense the signal molecules can be thought of as words within a language, each having a different meaning.

5. Quorum sensing in Vibrio fischeri Research into AHL (acyl-homoserine lactone) based quorum sensing started in the late 1960s. The marine bioluminescent bacteria Vibrio fischeri was being grown in liquid cultures and it was observed that the cultures produced light only when large numbers of bacteria were present (Greenberg, 1997). The initial explanation for this was that the culture media contained an inhibitor of luminescence, which was removed by the bacteria when large numbers were present (Kempner & Hanson, 1968). This was suggested because when grown in media "conditioned" by preliminary exposure to the bacteria, luminescence could be induced even at low cell densities. It was later shown that the luminescence was initiated not by the removal of an inhibitor but by the accumulation of an activator molecule or "autoinducer" (Nealson et al, 1970, Eberhard, 1972). This molecule is made by the bacteria and activates luminescence when it has accumulated to a high enough concentration. The bacteria are able to sense their cell density by monitoring the autoinducer concentration. This mechanism of cell density sensing was termed quorum sensing (QS). The molecule produced by V. fischeri was first isolated and characterised in 1981 by Eberhard et al. and identified as N-(3-oxohexanoyl)-homoserine lactone (3-oxo-C6-HSL). Analysis of the genes involved in QS in V. fischeri was first carried out by Engebrecht et al (1983). This led to the basic model for quorum sensing in V. fischeri which is now a paradigm for other similar quorum sensing systems. For many years following this, it was thought that AHL-based QS was limited to marine bacteria such as V. fischeri and V. harveyi. Research into antibiotic synthesis caried out at Nottingham and Warwick led to the discovery that QS was far more widespread than previously thought.

6. Antibiotic production in Erwinia carotovora In the early 1990s, Barrie Bycroft and Paul Williams from Nottingham and George Salmond from Warwick, were studying mutants of Erwinia carotovora that were unable to make carbapenem antibiotics. The idea was to find out which genes were defective in different mutants and so build up a picture of all the genes involved in the biosynthetic pathway. One class of mutants could not make antibiotics on their own but could do so when cross-fed by a second group of mutants. Investigations showed that the second type was supplying a signalling molecule which triggered antibiotic synthesis in the first group. The discovery was that the signalling molecule was the same as one used by a completely unrelated bacterium (V. fisheri) to trigger the emission of light (Bainton et al 1992). At this point, the researchers joined forces with Gordon Stewart, also at Nottingham, who had considerable experience of the signalling molecule used in bioluminescent bacteria.

7. Quorum sensing in Pseudomonas aeruginosa At around the same time, Gambello & Iglewski (1991) discovered that the human pathogen Pseudomonas aeruginosa also posesses a V. fischeri-like QS system. This was shown to regulate the production of elastase, an important virulence factor. The AHL responsible for the induction of elastase was identified as (3-oxo-C12-HSL)(Pearson et al, 1994). A second QS system regulating rhamnolipid, haemolysin and other important virulence factors was discovered by Latifi et al (1995). Winson et al (1995) showed that this system was responsible for the production of C4-HSL. This system was independently discovered by Ochsner et al (1994).

8. AHL-based QS in other species The discovery that bacteria other than marine Vibrios use AHL QS systems led to the development of biosensors that can detect AHLs from other bacteria (Swift et al 1993, Winson 1998). These sensors were used to detect QS systems in Enterobacter, Hafnia, Rahnella and Serratia. Since then, this and other methods have been used to identify a large number of other quorum sensing species. Follow the link below to see a list of bacteria with AHL-based QS systems. The molecular mechanisms underlying V. fischeri type QS systems are described in more detail in the V. fischeri system page.

9. Primeri različnih acil-homoserin laktonov

10. Gram positive bacteria have been shown to communicate using a number of different QS signals. Many employ post-translationally modified peptides created from larger precursors. These peptides are usually secreted by ATP-binding cassette (ABC) transporters. Some interact with membrane bound sensor kinases that transduce a signal across the membrane, others are transported into the cell by oligopeptide permeases, where they then interact with intracellular receptors. These systems are involved in the regulation of such diverse processes as virulence in Staphylococcus aureus, competence for DNA-uptake in Bacillus subtilis and Streptococcus pneumoniae, sporulation in B. subtilis, conjugal plasmid transfer in Enterococcus faecalis, and bacteriocin production in lactic acid bacteria (for reviews see Kleerebezem et al, 1997, Lazazzera and Grossman, 1998, Kuipers et al, 1998, Novick, 1999, Novick and Muir, 1999). A second signal molecule employed for QS in Gram positives is the butyrolactone. This is used by several Streptomyces species to control production of antibiotics and antibiotic resistance (Bibb, 1996) and aerial mycelium (Nodwell & Losick, 1998). In addition, it has recently be shown that many Gram positive bacteria have homologues of the LuxS protein from Vibrio harveyi. This is responsible for the production of the AI-2 signal molecule involved in QS in V. harveyi. Interestingly, no homologues of the recepters for AI-2 have been identified in Gram negative bacteria (or any Gram negative bacteria other than Vibrio species). The mechanism by which the AI-2 signal is recieved (if indeed it is recieved) is therefore unknown.

11. Can bacteria from one species communicate with those from another species? There is evidence that interspecies communication via QS can occur. This is referred to as quorum sensing cross talk. Cross talk has implications in many areas of microbiology as in nature bacteria almost always exist in mixed species populations such as biofilms.

12. What are the benefits of quorum sensing research? QS research has many potential applications, most of these involve controlling bacteria by interfering with their signalling systems. For example many bacteria rely on QS to control the expression of the genes which cause disease. If we can block the QS systems we may be able to prevent these bacteria from being dangerous.

14. Chromobacterium violaceum w.t. pigment violacein

15. Janthinobacterium lividum Chromobacterium violaceum CV026 Sev izloča AHL, ki ga spozna Chromobacterium v. in se zato ponovno prične sinteza violaceina.