Category Archives: medicine

On Quorum Sensing and Antibiotics

In your body, cells belonging to other organisms are more numerous than your own1. Most of these are not parasitic, we benefit significantly from some of our inhabitants. This is one of the reasons that traditional antibiotics are potentially harmful. Their action is indiscriminate, targeting both harmful and helpful bacteria. The wholesale killing off of our microbial boarders makes many vacancies, providing an opportunity for more virulent creatures to invade. As if this weren’t bad enough, left behind after a course of antibiotics are any bacteria that might have developed immunity to the drugs that put down their brethren. Thus, prescribing such medications also amounts to a selective pressure, an evolutionary nudge towards ever stronger infectors.

Once in your body, harmful bacteria must wait until their colony reaches a certain size for their attacks to be effective. This means that they must posses the ability to detect how many individuals of their species are present. Indeed, this behavior has been the subject of extensive research, and is referred to as Quorum Sensing (QS). The way this works is actually rather simple, each bacterium secretes a small molecule called an autoinducer (AI) at an approximately constant rate (in time and across individuals). Once the concentration of AI is high enough, the colony knows their population has risen to a level where the release virulence factors stands a good chance of successfully inducing pathology.


from reference 2

This example of cell-to-cell communication, in addition to providing a unique system to study such information transfer systems, presents an opportunity to attack unwanted microorganisms in a more species selective way. Thus avoiding both of the issues with antibiotics mentioned above.

Just such a feat was accomplished several years in the laboratory of Hiroaki Suga at SUNY Buffalo. This team of researchers was able to successfully reduce the virulence of Pseudomonas aeruginosa which is the main infectious killer of those with weakened immune systems, such as cancer, AIDS, and cistic fibrosis patients3. This was a great triumph, but another entry in this category has come along which further bolsters the case for attacking the bacterial-telegraph-system.

A group led by Kim Janda at Scripps was able to have a similar impact on Staphylococcus aureus. This bacteria is the main cause of infections in hospitals, and thus represents one of the strains most likely to evolve immunity to antibiotics4. Beyond this and in contrast to the earlier work, these authors were able to use antibodies to target the AIs, making the work potentially generalizable and inexpensive.

It is impossible to understate the beneficial effects that penicillin and it’s derivatives have had in western medicine. As we move forward, however, we must find ways to keep pace with our miniscule counterparts. These two examples of top notch research are exactly the kind of thinking that we need.

References

1. French, K. Randall, D & Burggren, W. (2001) Eckert Animal Physiology. W.H. Freeman

2. Waters, C.M. & Bassler, B.L. (2005) Quorum Sensing: Cell-to-Cell Communication in Bacteria. Annu. Rev. Cell Dev. Biol. 21:319–446

3. Smith, K.M. Yigong, B. & Suga, H. (2003) Induction and Inhibition of Pseudomonas aeruginosa Quorum Sensing by Synthetic Autoinducer Analogs. Chemistry & Biology 10:81-89

4. Park, J. Jagasia R. Kaufmann, G.F. Mathison, J.C. Ruiz, D.I. Moss, J.A. Meijler, M.M. Ulevitich, R.J. & Janda, K.M. (2007) Infection Control by Antibody Disruption of Bacterial Quorum Sensing Signaling. Chemistry & Biology 14:1119-1127