Biologists Yves Brun, Malcolm Winkler, Dan Kearns and Sidney Shaw have joined with chemists Michael VanNieuwenhze and Stephen Jacobson to analyze the cell walls of Bacillus subtilis, E. coli and Streptococcal pneumonia, some of the most studied bacteria that represent families of major pathogens that cause many human diseases.
Their recent advances involve using microscopic probes to tag single cells of bacteria with fluorescent dyes and observe each cell with high-resolution microscopes to better understand how bacteria build their cell wall, peptidoglycan.
Understanding how the cell wall is built and how it replicates and divides is the next step in new drug ?development.
“If you can see how something is being built, you have a better chance of being able to develop ways to interfere with the building process,” VanNieuwenhze said in a press release from the University.
Winkler, a professor of biology, specializes in S. pneumoniae and its increasing multidrug resistance. Winkler said cell walls have been the most druggable, or easily treated, part of any bacteria thus far. But that doesn’t mean the methods currently in effect will work forever.
“I think the cell wall is a complicated molecule. To really get progress and then push things along, you need to have teams of people working to solve problems nowadays, because the problems are hard,” he said. “But, the beauty of it is, the problems have always been hard but the technology is pretty ?amazing.”
IU’s Light Microscopy Imaging Center houses some of those new technologies, namely 3D-SIM microscopes that allow the research team to observe bacteria at high resolutions in three dimensions. In the past, that has been hard to do since bacteria like S. pneumoniae are one micrometer in diameter, or 0.00001 meters.
Using these microscopes, the team has found ways to chemically synthesize the fluorescent dyes so that they appear only when cells begin the process of replication.
“So, if that happens, then the only place you’re going to see fluorescence is where it binds. And that’s very cool,” Winkler said. “It will allow a lot of different kinds of experiments to be done much easier.”
Another goal of the project is to be able to synchronize the bacteria — basically, to hold the bacteria into little channels and watch a single cell tagged with these dyes divide from one to two to three to four to five in liquid ?medium.
“You can literally watch it happen in real time,” Winkler said.
“It’s a very large grant because it supports a couple different kinds of labs,” Winkler said. “It’s sort of one of the directions that I think some of the funding is going in. They want more investigative teams working on projects rather than having single labs kind of get together by accident. It’s really meant to be collaborative.”
The team has already begun to get results. Several studies that had started before the grant was being reviewed are in the process of being published fairly soon.
“Our goal is to understand the process at the fundamental level but also to shed light on the ways we can study and find new targets. As we understand the dynamics of these new tools, we may end up finding ways to inhibit peptidoglycan,” Winkler said.
