INFORMATIONAL HANDOUT: ________________________________________________________________ What is Cell Signaling? When we use this phrase, we are talking about the way cells communicate - using molecules that are produced, dispersed and then 'received.' In order to be the recipient of a chemical message, a cel must have specific receptors for the signaling molecule. The sensor may sit on the cell membrane - or it can be internal. In other cases, signals target specific sequences in the DNA where they bind (this is how some hormonal signals are received in your body). A signaling molecule binds to it's receptor by the old 'lock and key' method. The two molecules fit together in a way that allows them to tightly bind to one another. Other molecules don't fit, so they don't bind. Once a signal molecule is bound, it alters the shape or blocks some site on the receptor - which causes things to happen in the cell. A typical consequence is that a new protein gets transcribed or translated - or the transcription or translation of a protein is halted. Molecules of all shapes and sizes external to the cell. Some are signals, some are not. Those that are signals will target specific receptor molecules either on cell surface (red), inside cell (blue), or they may bind to specific sequences in DNA. Once bound to the target location, the receptor/signal complex causes some important change to occur. 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 signaling molecules which are released into the environment. As well as releasing the signaling 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 signaling 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 signaling 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. Why do bacteria talk to each other? QS enables bacteria to co-ordinate their behavior. As environmental conditions often change rapidly, bacteria need to respond quickly in order to survive. These responses include adaptation to availability of nutrients, defense against other microorganisms that may compete for the same Biology 215, Ruth A. Gyure Western CT State University nutrients and the avoidance of toxic compounds that are 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. Do all bacteria use the same signal molecules? Different bacterial species use different molecules to communicate. There are several different classes of signaling 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. 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. 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. Quorum sensing in Vibrio fischeri 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). At first, the behavior was misunderstood. It was later shown that the luminescence was initiated 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 something we refer to as an acyl-homoserine lactone (AHL). Analysis of the genes involved in QS in V. fischeri was first carried out by Engebrecht et al (1983), and this led to the basic model for quorum sensing in V. fischeri which is now the model 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 carried out at Nottingham and Warwick led to the discovery that QS was far more widespread than previously thought. Staphylococcus aureus and Pseudomonas aeruginosa, for example, both important human pathogens, have similar quorum sensing systems. ACKNOWLEDGEMENTS: University of Nottingham Quorum Sensing Site http://www.nottingham.ac.uk/quorum/introduction.htm Biology 215, Ruth A. Gyure Western CT State University