Biofilms with Bill Costerton

Bacteria that invade our bodies can do some surprising things — they form complex communities and talk to each other with chemical signals. Today — a scientist who’s using that information to develop new ways to fight back.

Bacteria cause many chronic illnesses in humans — from children’s earaches to cystic fibrosis.

New kinds of microscopes have revealed that a bacterium cell can change its behavior. Sometimes these cells are free-floating loners — and sometimes they come together to form intricate communities — called biofilms. Bill Costerton is the Director of the Center for Biofilm Engineering at Montana State University.

Bill Costerton: They have a genome, just like we do in every single cell … but they don’t express all their genes at the same time. They just express one set at one time, when they’re floating, and a totally different set when they settle down in a biofilm.

Sometimes bacteria turn on a set of genes that create the toxins that make us sick. At other times, those genes are turned off. That’s why some bacteria can be so resistant to antibiotics — the antibiotics can kill them only when certain genes are turned off. All this turning off and on of generes occurs as the bacteria release chemical signals.

Bill Costerton: Can we screw up their signals? Can we confuse them by counterfeiting their signals? Can we find out what the … gene expression is and jam that up?

Costerton and his team are trying to develop drugs that “talk” to bacteria — molecules that block the signals that tell bacteria when to release their toxins.

Mapping of 25 bacterial genomes that have been worked out in the past few years allow scientists to see whether genes are turned off or turned on.

Some excerpts from an interview with Dr. Costerton

  • The laser scanning confocal microscopy, lets just call it confocal, is a new technique, totally different from previous microsocpies because it actually has a laser beam coming down onto the surface and builds an image digitally…we don’t have to have glass slides and cover slips anymore. So if something has got bacteria growing on the surface, we can simply…put the laser to it, and get a lovely 3D image of the bacteria living on the surface.
  • And so basically, I had the idea when I saw all of this slime, that oh boy, the antibiotics are going to have trouble getting through that, and as often happens, I was completely wrong. I felt instinctively, that if they we behind all this slime the antibiotics wouldn’t be able to penetrate and then we did some nice engineering measurements and found that they penetrated very well, thank you very much. So turned out to be mostly the genetic differences so–we call them phenotypic differences, but what that really means is what set of genes is turned on at that particular moment. And that’s what makes them very resistant.
  • When bacteria are in small numbers somewhere, and they’re just getting a foothold and getting established, they’re busier than a one-armed paperhanger; they don’t waste any time making toxins or getting very aggressive, they just try to hunker down and survive. And then we they hit a certain numberâ they take a much more aggressive posture. And they do this by emitting a chemical…
  • What we could do in this case is to block that signal so that they do have enough to really get started getting nasty but we block the signal that says that they should start doing that, and we actually produce a molecule that looks a lot like the signal and jams up the whole machinery, and therefore they couldn’t react, they’d in fact have the more passive point of view and keep that strategy and probably the white cells would wipe them out just naturally.
  • So basically we know all of the genes in, oh, probably twenty or twenty-five important bacteria — so that’s really handy. We can see whether those genes are turned on or turned off.
  • The replacement of the old fuzzy light microscopes with the confocal laser scope is a fantastic advance. That really really set us up. And then all of the molecular techniques that let us identify bacteria and find out they’re there by looking for their DNA or RNA.
  • If you were thinking of the pace of bacterial research over a certain length of time and you had a curve slowly coming up, that doggone curve is going straight up right now.

What you have in your mind?