Friday, June 19, 2009

Quorum-Sensing Molecules

I was fascinated by Bonnie Brasler's TED talk on Quorum-Sensing, and being a chemist I wanted to know more about the molecules involved. She did put up a slide with structures during the talk, but I wanted more so I did a search on PubMed and found this Perspective written by Brassler and Michael Federle.
My only experience with the notion of a “quorum” is our Faculty Assembly where we sometimes have difficulty achieving a quorum. In order for the meeting to be “official” and for any votes taken to be valid we need to have a minimum number of faculty present, a “quorum.” For bacteria, quorum sensing is the way the bacteria “count” one another. The bacterium releases a particular molecule, called an autoinducer - if there are lots of the molecules, then there are a lot of bacteria. If there are very few autoinducer molecules, then there are few bacteria present. The bacteria has a protein receptor that binds to the autoinducer molecule – so the bacteria can “sense” the presence or absence of autoinducer molecules depending on whether or not the receptor protein has detected any. In this way the bacteria can change their behavior depending on the number of bacteria present, as measured by the number of autoinducer molecules it finds. As a group, the bacteria behave one way when there is a low density of bacteria present and a different way when there is a high density of bacteria present.
In the simplest examples, quorum-sensing allows the bacteria to switch between two different behaviors depending on the number of bacteria present. One example would be the staphylococcus aureus bacteria – at low density they adhere to the surface of the cells of the host organism where they can grow and produce more bacteria. Once they reach a “quorum” there are enough bacteria present to be able to invade the host cells Their metabolism then shifts from producing the proteins that allow attachment to the outside of host cells and starts to produce proteins and toxins that allow the bacteria to enter the host cells. The light-producing bacteria from Bonnie Brassler's TED talk produce light when there are a lot of bacteria present, and stop producing light when there are few bacteria present.
Enough about biology, what about the molecules involved? In this Perspective, two categories of autoinducers are discussed, and one “special case.” Gram negative bacteria produce a type of autoinducer referred to as AHL for Acyl Homocysteine Lactone. Different types of bacteria will have different acyl groups attached to the homocysteine, and only recognize their own type of AHL. Gram positive bacteria do not use AHL's, instead they produce specialized proteins called AIP for AutoInducing Peptides, which consist of a string of 5 to 17 amino acids, some of which may be modified. The two types of autoinducer (AI) are detected by the bacteria when the AI binds to a receptor molecule in the bacteria. The details differ, but when enough AI's are around to bind to their receptors, the receptor causes a change in gene expression in the bacteria, which leads to a different behavior by the bacteria. 

The AHL's and AIP's are species specific: each type of bacteria produces only one AI and only recognizes it's own AI. The third type of molecule discussed is an unusual boron-containing molecule that may have a role for communication between different species of bacteria. The light-producing bacterium vibrio harveyi produces two different autoinducer molecules. The first is referred to as AI-1. AI-1 is an AHL molecule used for communication only among the V. harveyi bacteria. The other autoinducer is AI-2 which, on the other hand, may have a role in allowing different species of bacteria to communicate with one another.

AI-2 is synthesized by the bacteria in three steps from S-adenosyl methionine. The enzyme for the final step in this synthesis is called LuxS and as it turns out the gene for LuxS is found in many different bacteria, which all seem to both make and respond to the presence of AI-2. The implication of this is that perhaps AI-2 serves as some sort of generic autoinducer that allows bacteria to sense not only their own species, but also all other species of bacteria that produce AI-2.
The really interesting thing is that if we understand how bacteria communicate, we can find ways to short-circuit that communication. Many pathogens use quorum-sensing to regulate their virulence. In the example I mentioned earlier about S. aureus, the bacteria depend on reaching a “quorum” before they begin to “invade” the host cells. If their ability to sense one another is prevented, then perhaps their ability to invade the host and cause disease could be reduced.

Federle, M. (2003). Interspecies communication in bacteria Journal of Clinical Investigation, 112 (9), 1291-1299 DOI: 10.1172/jci200320195


Unknown said...

AHL = N-acylated L-homoserine lactone

Steve W said...

Thanks for the correction. I don't know how I missed that.