The day started off with an amazing talk. To be honest, I knew less than nothing about bacterial quorum sensing and I’ve never really tried to learn about it. However, being at EB I thought I should expand my horizons and learn about something new. Some people might balk at an 8am start but if you slept in then you missed out on a phenomenal presenations. The speaker, Dr. Bonnie Bassler from Princeton University described how bacteria coordinate their activity so that they can accomplish more together than as individuals. The best analogy I have for this is in the movie Finding Nemo, when Nemo is caught in the tuna net and they all start swimming down together to escape. However, they need to reach a critical mass before making the switch. The question then became: how do they know how many bacteria are present and how do they know if they are all the same or if they are potential competitiors for resources. Quorum sensing is about taking a “chemical group vote” and then coming to a conclusion to change behavior if circumstances demand it. Many clinically relevant bacteria use this approach to be infectious as the change might be biofilm or virulence factor production.
Dr. Bassler then put quorum sensing in terms I could understand: it’s about signaling. The light bulb went on and I was hooked. Of course the light bulb was partially illuminated by the bright light of the culture of Vibrio cholera that she was showing on the screen. Vibrio bioluminesces when it reaches a certain concentration as a response to quorum sensing. With a clear reporter it was possible to determine the rules for the conversation: which molecules secreted by the bacteria were for intraspecies communication, which were for intragenera communication, and which were for interspecies communication.
Identification of the genes involved revealed a soluble factor and membrane receptor that are involved in the signaling. The genes of the lux operon include a 9 transmembrane domain receptor (just 2 too many!) that has been “persnickety”, to use Dr. Bassler’s word, to crystalize. They have been able to use a number of molecular genetic approaches to characterize the receptor, but the structural work is still not there. However, a different species of bacteria, Chromobacterium violaceum, uses a similar soluble factor for quorum sensing. It became apparent to Bassler and her colleagues that if the soluble factors are similar, that the receptors must be similar too. The CviR (the receptor for quorum sensing in C. violaceum) is soluble, which made it much more suitable for crystallography and biochemical approaches. Of course it only turns purple instead of bioluminescing, so it’s not nearly as cool! One of the things I took away from this is the fact that evolution never wastes a good thing. Although Dr. Bassler didn’t address this specifically, it is very reminiscent of the way estrogen receptors have both cell-surface and intracellular receptors. With structural and molecular information, it is now possible to develop therapeutic interventions to block quorum sensing in pathogens, and Dr. Bassler described how they are moving in that direction.
The last part of the talk focused on the idea that bacteria do not live growing in a swirling culture in nature the way we grow them in the lab; they grow on solid surfaces. To get a real appreciation for them we need to see how they change and behave on solid surfaces. What kind of solid surfaces? How about in a stent used for cardiac patients? Dr. Bassler described how physicists and engineers view biomedical problems through very different lenses and can inform the types of questions we ask and how we ask them. This allowed her to really investigate how quorum sensing leads to biofilm formation and how that leads to stent blockage.
If you want to learn more about Dr. Bassler and her research here are a few good links to get you started: