Electron Microscopy and Fighting Superbugs

Last week, a bunch of news articles came out (like this one) that talk about how we are on track to figuring out new ways to tackle antibiotic resistant superbugs. The research they are referring to highlights a paper recently published in Nature (a closed access journal) by Changjiang Dong’s group at the University of East Anglia. To my delight, this discovery is more of a physics victory than a microbial biology one. Given my background in Physics, I’ll take this as an opportunity to tell you about how the microscope used in this research works.

The Diamond Light Microscope sounds fancy, but it’s not a new technology; it’s the same cryo-electron microscopy that has been used for decades. It works by launching really fast electrons at a sample and then using very sensitive detectors and mathematical magic to map how the electrons bounce off of the surface. The power source required to launch the electrons uses up to 300 kV, which is pretty standard for many electron and ion beam microscope technologies. The elctron beam is aimed down a large column (in a strong vacuum) in which ‘lens’, in this case voltages, are used to shape and steer the beam to hit a sample in a very specific way. When electron beams are moving as fast as they do under 300kV of power, a large column is needed to steer and shape the beam because the lens can only be so strong. That is why the Diamond Light Microscope is so much bigger than your typical Electron Microscope, which uses much less than 300kV. The stronger the beam, the better resolution you can get of your sample.

But wait, how do you keep a 300kV electron beam from obliterating your sample? That’s where the cryo part comes in! By keeping a sample really cold, you can pull out energy from the system fast enough that the beam doesn’t melt the sample. Cryo freezing techniques are now so fast that we can freeze biological specimens in action and then image them in that state. With the amazing resolution we get from a 300kV source, we are able to image extremely tiny things like viruses or proteins. But to get such high-resolution images, the software engineers are the ones deserving the credit; they are the ones who have designed the software and detectors sensitive enough to transform bagillions of electrons bouncing off of a surface into an image.

So, back to the paper. Dong’s team used this awesome cryo EM technology to image the BAM complex, which is the beta barrel assembly machinery that crosses through the periplasmic space in the membranes in all gram negative bacteria. If we can figure out the details and structure of how this assembly keeps gram negative bacteria alive, then we can figure out how to disturb it in order to kill the cell. Given that gram negative bacteria can be superbugs, we are on track to a new way to fight antibiotic resistant superbugs. While the news headlines scream ‘awesome discovery!’, it turns out the microscope technology isn’t all that new, and the BAM complex is already well studied. That said, it’s still pretty cool. And claiming to find ways to tackle superbugs sounds like a sure way to get funding…