Turned up to eleven: Fair and Balanced

Wednesday, February 22, 2006

Biofilms, Quorum Quenching, and Antibiotic Resistance
It's been a rough couple of weeks (in a good way), but here's another installment of our saga. As we learned last week bacteria often form Biofilms, aggregates on surfaces that can cause lots of trouble. I didn't get too much into the details of how these aggregations form, but I a couple of points; 1) Biofilms play major roles in lots of things we aren't to happy about, and 2) Biofilm formation is controlled by chemical signals that bacteria produce. I mentioned bacteria forming biofilms as part of pathogenesis. Another bit of bad new is that Biofilms are more resistant to antibiotics than their planktonic (free floating) counterparts.

The ways in which bacteria cause us problems are manifold. For example, when someone goes into the hospital, they often come out with an infection they didn't have before. One of the very common ways this occurs is when bacteria grow in a biofilm on one of the various invasive catheters used commonly in medicine. These include urinary catheters (UTIs are very common, although usually not fatal) and lines into the bloodstream (much more dangerous). This problem is exacerbated by the well known fact that bacteria that colonize hospital workers are much more likely to be resistant to antibiotics (an aside; when I was a grad student, we did this experiment with the med students I was teaching. The ones who were currently working in the hospital had bacteria on their skin with higher levels of resistance to common antibiotics). This is even more problematic when we recall what I mentioned one paragraph ago, that biofilm bacteria are even more resistant.

So this leaves us with the following scenario; patient comes to hospital, gets an infection from a catheter, gets treated with antibiotic, then another, then another, till they eventually get vancomycin and get better. So now all their associated bacteria have been exposed to a very strong antibiotic. At a population level, this can lead to the emergence of vancomycin resistance in bacteria (like MRSA) that are resistant to virtually everything else.

Can this get worse? Oh, yes! Bacteria in biofilms (like the ones commonly causing these infections) are not terribly picky about their neighbors. Single species biofilms are cultivated in laboratories, multiple species biofilms are found in nature (such as dental plaque). So when a multiple species biofilm occurs, DNA transfer can occur. And does it? Hoo boy, does it ever!

So, to recap; bacteria in biofilms cause diseases, especially in hospitals, where antibiotic resistance is a bigger problem. Oh yeah, and biofilm bacteria are even more resistant.

So how to deal with this?
Well, in the last few years (about 5, give or take), a lot of investigators (including me, briefly) got interested in the idea of Quorum Quenching. The basic idea goes like this. A QS circuit involves a signal that is detected by a protein on the surface or in the cytoplasm (a receptor). The receptor either directly influences gene expression (a regulatory protein, or response regulator) or signals to a downstream protein that does this (Bonus points to people who recognize the similarity to hormone systems). So interfering with this would presumably prevent expression of genes that are regulated by quorum sensing (virulence factors and biofilm formation factors, to name a few). Two basic approaches have been attempted, with some success in vitro and in planta. Competitive inhibition with molecules (furanones) that bind to the receptors (perhaps you have heard of the analogous notion of estrogen-like molecules contaminating water and interfering with hormonal cycles of animals and humans), and enzymatic degradation of the signal (I worked on this type of thing). The basic notion is that if we can prevent biofilm formation, we can reduce the levels of biofilm related disease, and therefore 1) make people's lives better, and 2) reduce the use of antibiotics. So, how's it going? Well, I'm out of the business, so I can't really answer that. It's promising, and it will be very likely to work in industrial and agricultural settings, but in medicine, we'll see.