The DNA Files: Biofilms

In 2007, WSKG Radio aired a series of reports on genetic science research in our region.

Crystal Sarakas spoke with Dr. David Davies about his research into colonies of bacteria, called biofilms, and what effect that research may have in the future.

 

We've all heard of bacteria, single-cell micro-organisms that are found just about everywhere on earth and play a number of roles, both good and bad. But few of us have heard of biofilms, and just like regular bacteria, biofilms are everywhere.

"Wherever you see slime in the movies dripping from the walls or in the shower dripping from your curtain - that's a biofilm."

That's Dr. David Davies, a microbiologist at Binghamton University. He studies these slimy colonies of bacteria known as biofilms. But, what exactly are biofilms?

Biofilms are colonies of bacteria that attach to a surface and then excrete a protective and adhesive matrix that allows them to stay put. You've probably encountered them hundreds of times in your life. Those slippery, slime-covered rocks on the bottom of a stream-bed or the film that forms on standing water. The plaque that forms on your teeth. Those are all biofilms. Just like planktonic -or free-floating bacteria - biofilms have their good side and their bad side. It's the bad side of these biofilm colonies that Dr. Davies is concerned with, namely infections.

"Biofilms cause infections that can be problems. Inner ear infections or bladder infections, prostate infection, etc. Acne is a biofilm infection. There are a number of instances of biofilm infections, but all of them share the commonality that they don't respond well to treatment with antibiotics. Generally it's considered that a biofilm infection requires a 100 to1000 times greater concentration of antibiotics to treat compared to a systemic planktonic infection. Biofilms do not respond well to therapy. So, typically a biofilm infection either has to resolve itself as a consequence of the immune system clearing it or it has to be removed surgically."

The current treatment for biofilm infections, particularly skin infections that are common in advanced-stage diabetes, range from mass doses of antibiotics that may or may not work to wound debridement.

"Typically a dremel-type tool is taken - like a dentist's drill - and is used on 40,000 or so rpm to scoop away, to carve out the tissue around the infection and to get to fresh, uninfected tissue. Then, basically at that point both patient and physician pray that the fresh tissue will not become infected with the organism and that the wound will resolve itself. Unfortunately, in many cases that doesn't occur. Particularly in advanced stages of diabetes one of the outcomes is amputation. This is one of the things that we are really trying hard to combat."

"What we really need to do is, for instance in the case of a diabetic patient, is to reach the tipping point where the outcome of an infection favors the patient's survival rather than the survival of the microorganism. In doing that - what kinds of strategies might be available? Well, in thinking about these infections as biofilm infections which is becoming more and more apparent, there's a requirement for a new kind of thinking about how to reach that tipping point. Antibiotics just don't do it by themselves. So we have to figure out a novel strategy to manage the bacteria so that either antibiotic treatment or the immune system or both in combination can tip the balance in favor of the patient's recovery."

Scientists have been searching for years for a way to combat these infectious biofilm colonies. The slime that surrounds the biofilms protects them, preventing both the body's own immune system and antibiotics from coming into contact with the bacteria that make up the colonies. But recent research by Dr. Davies may change that. He's discovered a molecule that, when introduced to these biofilm colonies, provokes certain genetic and physiological changes in the bacteria which causes them to disperse and return to their ndividual state where the bacteria is much more susceptible to treatment.

" What we've done is look at the behavior of biofilms as they develop in nature and noticed that one of the common features of all biofilms is that as they get older the bacteria from these dense cell clusters get up and disperse. They leave the biofilm as it becomes overcrowded. It turns out that they leave in response to signals that are produced by the bacteria in the biofilms. These signals build up as the cell density in the biofilm gets higher and higher. So it makes sense for a bacterium to leave because as the biofilm becomes more and more dense it becomes less probable that a bacterium in the center of a cell cluster will survive, lacking food and suffering from an accumulation of waste products. So here we are looking at a natural process thinking to ourselves - how can we subvert this process or take advantage of this process and use it to help tip the balance in an infection? We spent a long time in trying to recover and then identify and characterize this agent that is responsible for inducing discursion in bacteria. Over the past year we actually completed our work on the molecular characterization of this compound."

The molecule that Dr. Davies has isolated has been tested against a number of biofilm infections and has proven to be effective in dispersing biofilms containing the bacteria that cause strep, E. coli, and staph infections.

"We now know that we have a chemical that we can add to essentially any biofilm. It works not just on the organism we isolated it from, but all bacteria we've tested it against. It induces these bacteria, regardless of their stage of biofilm development, to disperse from the biofilms. So the idea is that we could take this chemical and then apply it to an infection and induce the bacteria to transition from a biofilm mode of growth to a planktonic mode of growth. These planktonic bacteria are fairly easily taken care of by antibiotics and or the immune system."

There are many possible medical applications for this new method of dispersing biofilm colonies, but one that Dr. Davies is particularly interested in is the treatment of non-healing wounds.

"Non-healing wounds might not be life-threatening to a patient in many cases, but what they do to the quality of life is profound. People losing mobility, being unable to or embarrassed to leave their homes, unable to go out and go on a hike, a walk, a bike ride really enjoy themselves because they are bedridden or restricted to a wheelchair. There's no reason an 80-year-old person with diabetes shouldn't be out playing soccer. This is what we should be working on and this is what we are working on. We want to be able to go in and instead of practicing wound debridement, we want to go in and treat these non-healing wound infections infected with biofilms, successfully have them heal and have these people get up and walk again. Don't amputate their feet, heal them so that they can walk around and have a good quality of life."

Guests: 
Dr. David Davies