OPED31 Quorum Sensing

Many illnesses are caused by bacterial infection (e.g. meningitis, diphtheria, etc.) and the standard treatment is to use drugs called antibiotics that kill and destroy these bacteria. A problem with this approach is that resistance to antibiotics slowly increases due to natural selection - as the drugs kill the vast majority of the bacteria some may survive due to genetic differences, and these survivors are the ones around to multiply and pass on their resistance. For example, Staphylococcus aureus is a bacterium that causes infections in hospitals. The first antibiotic used on this bug was Penicillin. As resistance to this drug began to emerge the antibiotic methicillin was developed. Eventually S. aureus began to show resistance to methicillin, and in these cases the drug vancomycin was used. Now resistance to this drug has been seen to occur.

Research has shown that disease-causing bacteria operate in two modes, a 'quiet' mode when they are present but do not show much activity and an 'active' mode in which they attack the host system. It is theorized that when bacteria are present in low numbers they remain quiet, and only turn virulent when they are present in large enough numbers to overwhelm the hosts' immune system response. The mechanism which these bacteria use to gauge their numbers is known as Quorum Sensing. Each bacterium secretes a small amount of a chemical for which it has surface receptors... The larger the number of bacteria present the higher the level of the chemical, and this is detected by the surface receptors. When they detect that sufficient numbers are present (a "quorum") they start attacking their host.

The presence of this mechanism suggests that an alternate method might be used to defend against these bacteria. Instead of using drugs to kill them, drugs might be developed that disrupt their signalling mechanisms (e.g. by interfering with the production of their sensing chemical, by breaking down the chemical in the blood, or by blocking their surface receptors) so that they do not turn virulent but remain quiet as they do not detect a quorum. This would allow the hosts' immune system sufficient time to destroy the bacteria on its own. This approach also would seem to be less likely to result in the development of selective resistance, so that this class of drugs might last much longer than conventional antibiotics. One potential difficulty with this new approach is that if the quorum sensing systems are different among different bacteria then drugs developed would only work against a specific bacterium. However, some promising research at Princeton University has suggested that a single quorum sensing mechanism may be in use by most bacteria, and that bacteria have both a species-specific and a universal mechanism.

Currently most research in this field is being done by smaller biotech firms, it is to be hoped that big pharma can break out of its current paradigm and pursue this new approach...

© SNi 02/02/03