In SPIN
Ireland's science wildlife and discovery magazine
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Science Spin September 2008
How to beat the 'superbugs'
As we reach the 80th anniversary of Fleming's discovery of penicillin; the wonder drug which heralded a new era in the fight against infection, the medical establishment is now faced with a new challenge in the form of antibiotic resistance - the bugs are fighting back! Moreover, the superbugs, such as MRSA (meticillin resistant Staphylococcus aureus) and C. diff (Clostridium difficile) appear to be winning.
Dr Roy Sleator, pictured here, is a Health Research Board and Alimentary Pharmabiotic Centre Principal Investigator.
With life-cycles measured in minutes rather than years, bacteria have an extraordinary ability to evolve and adapt rapidly to changes in their environment. Thus, in a world where only the fittest survive those bacteria which have developed resistance to antibiotics will predominate. This is particularly apparent in hospital environments where bacteria are constantly exposed to different antibiotics; such repeated exposure has facilitated to the development of multiple antibiotic resistance and what we now refer to as hospital acquired or nosocomial infections.
Struggle
Faced with an emerging pandemic of antibiotic resistance, clinicians and scientists alike are now struggling to find viable therapeutic alternatives to our failing antibiotic wonder drugs.One such alternative may be provided by the bacteria themselves.This "fighting fire with fire" approach involves what is known as probiotic therapy - the application of so called "good bugs" for therapeutic effect.
Many disease causing bacteria, the pathogens, exploit oligosaccharides occurring on the surface of host cells. These are carbohydrates made up of sugars, and they serve as receptors for toxins that enable the pathogen to enter the host cell. Blocking the adherence of the oligosaccharide receptors prevents infection because it makes it more difficult for the pathogen to take up residence. The pathogen can then be overcome by the immune system.
'Designer probiotics' have been engineered to express receptor-mimic structures on their surface. These 'fool' the pathogen by attracting it to the wrong target. When administered orally, these engineered probiotics bind to and neutralize toxins in the gut lumen and interfere with pathogen adherence to the intestinal epithelium - thus essentially "mopping up" the infection.
In addition to infection control, probiotics are also being engineered to function as novel vaccine delivery vehicles. These have the advantage of stimulating the immune system without the danger of toxicity which can be a problem with vaccines based on live attenuated pathogens.
Probiotic vaccine carriers administered orally, or by nasal spray, enter the body through the mucose membranes. This mimics natural infections, and leads to longer lasting response. Mucosal vaccine delivery has a lot of other advantages. It reduces the pain and possibility of cross contamination associated with intramuscular injections, and medically trained personnel are not required to administer the vaccine. This is a big consideration for large scale vaccination projects in less well developed countries.
When the rock band, The Verve, gave us the immortal words "Now the drugs don't work, they just make you worse," they may have been thinking about antibiotic resistant "super bugs". It could well be that engineered "good bugs" can be our allies in winning that war.
