Sunday, November 23, 2008

Extracellular Membrane Vesicles in Bacteria: Taking Quorum Sensing in New Directions

ResearchBlogging.orgBacterial quorum sensing is not a new phenomenon by any means. Although the term has only recently come into the existence, the concept has been around for decades.
Bacterial communication has become much more sophisticated than previously thought
In 1964,Tomasz and Hotchkiss, out of Rockefeller, demonstrated the presence of a macromolecule responsible for induction of competence in pneumococcus when the cells reached a specific growth point in mid to late log phase.
This concept has been vastly expanded upon and the ramifications of such diffusible communication molecules are vast. Everything from biofilm formation to stringent responses to bioluminescence have been shown to be controlled by quorum (or diffusion) sensing molecules.

Commonly, quorum sensing molecules are lactones, small peptides, or small lipids. It is thought that these small molecules are secreted by the cell and diffuse through the aqueous environment where they can interact with other cells. This is all well and good, IF the molecule of interest is hydrophillic and freely diffusible. But researchers are finding that many quorum sensing molecules are NOT hydrophillic, and instead very hydrophobic, such as a quinilone with a long chain fatty acid attached. One such example of this, is the Pseudomonas aeruginosa molecule called PQS.

How can a molecule be used as an extracellular signal, if it can not diffuse freely? Dr. Marvin Whitely and colleagues have shown that PQS is able to promote the formation of membrane vesicles off the outer Pseudomonas memPseudomonas may be interacting with our cells in ways we haven't even thought of  yetbrane. Pseudomonas is known to naturally produce these vesicles, however PQS directly induces changes in the lipid membrane to form such vesicles.

Furthermore, these vesicles have the strong potential to be able to capture a variety of macromolecules that are in the vicinity of the membrane bleb. A prime example would be the beta-lactamases that are in the periplasmic space. But we could imagine other molecules being packaged up and delivered.

Molecules that are packaged could be delivered to the same cells in the population, or to foreign cells of different species, perhaps even to humans during pathogenesis. The possibilities are endless as to what these membrane vesicles could be providing instructions for.

One very important piece of data that is missing from this model, is that researchers have yet to observe membrane vesicles of one cell fusing with another cell. This would provide solid evidence that these vesicles could, in fact, deliver signals to other cells.

I had the privilege to have Dr. Whitely as a guest lecturer recently. He has some very interesting work on going in his lab, including the amazing creation of bacterial lobster traps. This work is not yet published, so I should not say anymore than that. However, once it is in the public domain, it has the potential to revolutionize the study of small bacterial populations.

1) Tomasz and Hotchkiss. "Regulation of the transformability of Pneumococcal cultures by macromolecular cell products." PNAS (1964). 51, 3. p480

2)Mashburn, L., & Whiteley, M. (2005). Membrane vesicles traffic signals and facilitate group activities in a prokaryote Nature, 437 (7057), 422-425 DOI: 10.1038/nature03925