Quorum Sensing and Disease
Much has been learned in the past decade about the complex behavior of bacteria under the influence of various Quorum Sensing systems. Many bacteria possess multiple QS systems, which control different aspects of virulence or other behaviors at different times in the infection process. And each bacteria species responds differently to QS stimuli, depending on environmental pressures, the presence or absence of competing bacterial species, the immune response of the host and other conditions.
For example, many bacteria form dense collections of cells called biofilms that are enclosed in a protective barrier. Such biofilms are highly resistant to host immune responses, anti-bacterial agents and other threats. The creation of these biofilms is regulated by qs signaling, and they generally are created after very large numbers of bacteria are present.
Some bacteria, however, use quorum sensing to end the biofilm stage as well as begin it. Cholera is one such example. In the final stages of infection, cholera uses QS signaling to dissolve existing biofilms and begin a massive dispersal of individual bacteria. This creates a highly infectious condition within the host and aids in cholera’s ability to spread.
There are many such examples of different bacteria responding to QS signaling in diverse ways at different times during the infection process. What seems to be nearly universal, however, is the bacteria’s tendency to maintain as low a profile as possible when the host is first infected. It is believed that this behavior minimizes the host’s immune response while the bacteria build sufficient numbers to mount an effective offense. When a sufficient number is reached, the bacteria manifest their pathogenic (disease causing) arsenal. The timing of this transition reveals an exquisite genetic intelligence: when pathogenic bacteria have reached a density that would trigger the host’s full-scale immune response whether or not there existed a disease symptom stimulus, the bacteria, using QS signaling, begin their disease-causing phase. The disease stresses the host, thereby weakening the host’s ability to respond to the infection. This gives advantage to the bacteria.
The second, nearly universal trait, is that even after a bacterium has entered its pathogenic phase, it quickly returns to its non-pathogenic state when we disable its QS mechanisms. This is another clear sign of genetic intelligence, for when a bacterium in its pathogenic state is passed on to a new host, the new host would quickly locate and dispatch the invader if the invader continued in its pathogenic form. What happens when such transfers do occur is that, from the bacterium’s point of view, there is an immediate cessation of the quorum. This is the indication to the bacterium that it is in a new host, and that the infection process is starting over. All pathogenic activities of the bacterium then cease, giving the bacterium time to multiply and, later, mount another offense. This is the beauty of the anti-QS approach to the treatment of infection. It terminates the disease causing activities, thereby returning the body to strength and health. The body can then deal with the infection through its normal immune system responses, without inflammation or other deleterious effects. In contrast, current antibiotic treatments attempt to kill the bacteria while the body is in a state that is already compromised by the disease. The combination of the disease and the stress caused by many antibiotics can further weaken the system to dangerous levels.
Ideally, anti-quorum sensing treatments would be initiated prior to the bacteria becoming pathogenic. However, this is generally not practical due to the absence of symptoms prior to pathogenesis. In other words there is likely no indication of infection and therefore no call for treatment. The exception to this might be cuts, scrapes or open wounds. The prevalence of Staph and other infectious agents on the skin and in the environment, especially in light of the antibiotic resistant strains that are rapidly spreading, might suggest preventive treatments with anti-QS agents. But in any case, treatment after pathogenesis has occurred is still effective.