Bacterial Communication: Quorum Sensing in Bacteria
Bacteria can behave either as individual single-celled organisms or as multicellular populations. Bacteria exhibit these behaviors by chemically "talking" to one another through a process called quorum sensing. Quorum sensing (def) involves the production, release, and community-wide sensing of molecules called autoinducers (def) that modulate gene expression, and ultimately bacterial behavior, in response to the density of a bacterial population.
To initiate the process of quorum sensing, bacterial genes code for the production of signaling molecules called autoinducers (def) that are released into the bacterium's surrounding environment.These signaling molecules then bind to signaling receptors either on the bacterial surface or in the cytoplasm. When these autoinducers reach a critical, threshold level, they activate bacterial quorum sensing genes that enable the bacteria to behave as a multicellular population rather than as individual single-celled organisms (see Fig. 1). The autoinducer/receptor complex is able to bind to DNA promoters and activate the transcription of quorum sensing-controlled genes in the bacterium. In this way, individual bacteria within a group are able to benefit from the activity of the entire group.
1. In Gram-negative bacteria, the autoinducers are typically molecules called acyl-homoserine lactones or AHL. AHLs diffuse readily out of and into bacterial cells where they bind to AHL receptors in the cytoplasm of the bacteria. When a critical level of AHL is reached, the cytoplasmic autoinducer/receptor complex functions as a DNA-binding transcriptional activator.
2. In Gram-positive bacteria, the autoinducers are oligopeptides, short peptides typically 8-10 amino acids long. Oligopeptides cannot diffuse in and out of bacteria like AHLs, but rather leave bacteria via specific exporters. They then bind to autoinducer receotors on the surface of the bacterium. When a critical level of oligopeptide is reached, the binding of the oligopeptide to its receptor starts a phosphorylation cascade that activates DNA-binding transcriptional regulatory proteins called response regulators.
The outcomes of bacteria-host interaction are often related to bacterial population density. Bacterial virulence, that is its ability to cause disease, is largely based on the bacterium's ability to produce gene products called virulence factors that enable that bacterium to colonize the host, resist body defenses, and harm the body.
At a low density of bacteria, the autoinducers diffuse away from the bacteria (see Fig. 2). Sufficient quantities of these molecules are unable to bind to the signaling receptors on the bacterial surface and the quorum sensing genes that enable the bacteria to act as a population are not activated. This enables the bacteria to behave as individual, single-celled organisms.
Possible advantages of individual bacterial behavior:If a relatively small number of a specific bacterium were to enter the body and immediately start producing their virulence factors, chances are the body's immune systems would have sufficient time to recognize and counter those virulence factors and remove the bacteria before there was sufficient quanity to cause harm. The bacterium instead utilizes genes that enable it to act as an individual organism rather than as part of a multicellular population.
Acting as individual organisms may better enable that low density of bacteria to gain a better foothold in their new environment in the following ways:
1. Many bacteria are capable of motility and motility serves to keep bacteria in an optimum environment via taxis (def).
Motility and chemotaxis probably help some intestinal and urinary pathogens to move through the mucous layer so they can attach to the epithelial cells of the mucous membranes. In fact, many bacteria that can colonize the mucous membranes of the bladder and the intestines are motile. Motility probably helps these bacteria move through the mucus in places where it is less viscous.
2. One of the body's innate defenses is the ability to physically remove bacteria from the body through such means as the constant shedding of surface epithelial cells from the skin and mucous membranes, the removal of bacteria by such means as coughing, sneezing, vomiting, and diarrhea, and bacterial removal by bodily fluids such as saliva, blood, mucous, and urine. Bacteria may resist this physical removal by producing pili (def) (see Fig. 3), cell wall adhesin proteins (def) (see Fig. 4), and/or biofilm-producing capsules (def). Some pili, called type IV pili also allow some bacteria to "walk" or "crawl" along surfaces to spread out and eventually form microcolonies.
Movie of twitching motility of Pseudomonas Courtesy of Dr. Howard C. Berg from the Roland Institute at Harvard. |
Scanning electron micrograph E. coli with pili; courtesy of Dennis Kunkel's Microscopy.
3. Many bacteria secrete an extracellular polysaccharide or polypeptide matrix called a capsule or glycocalyx that enables the bacteria to adhere to host cells, resist phagocytosis, and form microcolonies (def).
As the bacteria geometrically increase in number by binary fission, so does the amount of their secreted autoinducers, and production of high levels of autoinducers then enables the population of bacteria to communicate with one another by quorum sensing.
At a high density of bacteria, large quantities of autoinducers are produced (see Fig. 5) and are able to bind to the signaling receptors on the bacterial surface in sufficient quantity so as to activate the quorum sensing genes that enable the bacteria to behave as a multicellular population (see Fig. 1).Advantages of multicellular behavior:
1. By behaving as a multicellular population, individual bacteria within a group are able to benefit from the activity of the entire group. As the entire population of bacteria simultaneously turn on their virulence genes, the body's immune systems are much less likely to have enough time to counter those virulence factors before harm is done.
2. Virulence factors such as exoenzymes and toxins can damage host cells enabling the bacteria in the biofilm to obtain nutrients.
3. As the area becomes over-populated with bacteria, quorum sensing enables some of the bacteria to escape the biofilm and return to individual single-celled organism behavior in order to find a new sight to colonize.
Pseudomonas aeruginosa is an example of a quorum sensing bacterium. P. aeruginosa causes severe hospital-acquired infections, chronic infections in people with cystic fibrosis, and potentially fatal infections in those who are immunocompromised.
1. P. aeruginosa first enters the body functioning as individual bacteria. Motility genes (coding for flagella) and adhesin genes (coding for pili and cell wall adhesins) are expressed. The flagella enable the initial bacteria to swim through mucus towards host tissues such as mucous membranes. Pili then enable the bacteria to reversibly attach to host cells in order to resist flushing and begin colonization (See Fig. 6A). Type IV pili, which enable a twitching motility in some bacteria, then enable the bacteria as they replicate to crawl along and spread out over the mucous membranes (See Fig. 6B). The pili subsequently retract and bacterial cell wall adhesins enable a more intimate attachment of the bacterium to the mucous membranes (See Fig. 6C).
2. Once P. aeruginosa is able to replicate and achieve a high population density, quorum sensing(See Fig. 6D), biofilm formation, and the production of virulence exoenzyme and toxins. The high density of bacteria bacteria are now acting as a multicellular population rather than as individual bacteria.
Biofilms (def) are groups of bacteria attached to a surface and enclosed in a common secreted adhesive matrix. Many pathogenic bacteria, as well as normal flora and most environmental bacteria, form complex bacterial communities as biofilms. The biofilm enables bacteria to:
- resist attack by antibiotics;
- trap nutrients for bacterial growth and remain in a favorable niche;
- adhere to environmental surfaces and resist flushing;
- live in close association and communicate with other bacteria in the biofilm; and
- resist phagocytosis and attack by the body's complement pathways.
Electron micrograph of a biofilm of Haemophilus influenzae from Biomedcentral.com
Scanning electron micrograph of dental plaque.© H. Busscher, H. van der Mei, W. Jongebloed, R Bos, authors. Licensed for use, ASM MicrobeLibrary.
The exoenzymes and toxins damage host cells enabling the bacteria to get nutrients. (See Fig. 6E, and Fig. 6F)
3. When the population of P. aeruginosa begins to outgrow their local environment, quorum sensing enables them to turn off adhesin genes and turn on flagella genes that allow some of the bacteria to spread out of the biofilm to new location within that environment via motility (See Fig. 6G and Fig. 6H).
It turns out that bacteria are multilingual. They use quorum sensing not only to "talk" to members their own species (intraspecies communication), but also to "talk" to bacteria that are not of their genus and species (interspecies communication). Intraspecies autoinducers and receptors enable bacteria to communicate with others of their own species while interspecies autoinducers and receptors enable bacteria to communicate with bacteria of a different species or genus (see Fig. 7). The autoinducers for interspecies communications are referred to as AI-2 family autoinducers and are different from the intraspecies (AI-1) autoinducers. In some cases bacteria use interspeciecies communication to work cooperatively with various other bacteria in their biofilm to the benefit all involved; in other cases, bacteria may use interspecies communication in such a way that one group benefits at the expense of another.
Furthermore, bacteria are capable of interkingdom communication, communication between bacteria and their animal or plant host. Increasing numbers of bacteria are being found that have signaling receptors that recognize human hormones. For example, a number of bacteria that are pathogens of the human intestinal tract have a sensing molecule called QseC that binds the human hormones adrenaline and noradrenaline. This, in turn, activates various virulence genes of the bacteria. On the other hand, some bacterial autoinducers can enter human host cells and regulate human cellular function. For example, at low concentration some bacterial autoinducers supress host immune responses thus better enabling those bacteria to better establish themselves in the body. At high concentrations, however, they stimulate an inflammatory response in the host to help the bacteria to spread from the initial infection site. One bacterial autoinducer has been found to initiate apoptosis (cell suicide) in phagocytes such as neutrophils and macrophages.
To hear a talk by Dr. Bonnie Bassler, one of the pioneers in bacterial quorum sensing, go to the following link: http://www.ted.com/talks/bonnie_bassler_on_how_bacteria_communicate.html.
