A clever new imaging technique discovered at the University of California, Berkeley, reveals a possible plan of attack for many bacterial diseases, such as cholera, lung infections in cystic fibrosis patients and even chronic sinusitis, that form biofilms that make them resistant to antibiotics.

By devising a new fluorescent labeling strategy and employing super-resolution light microscopy, the researchers were able to examine the structure of sticky plaques called bacterial biofilms that make these infections so tenacious. They also identified genetic targets for potential drugs that could break up the bacterial community and expose the bugs to the killing power of antibiotics.

"Eventually, we want to make these bugs homeless," said lead researcher Veysel Berk, a postdoctoral fellow in the Department of Physics and the California Institute for Quantitative Biosciences (QB3) at UC Berkeley.

Berk and his coauthors, including Nobel laureate Steven Chu, report their findings in the journal Science.

"In their natural habitat, 99.9 percent of all bacteria live as a community and attach to surfaces as biofilms; according to the National Institutes of Health, 80 percent of all infections in humans are related to biofilms," Berk said.

The researchers were able to employ new techniques that allowed them to zoom into a street-level view of these biofilms, where they learned "how they grow from a single cell and come together to form rooms and whole buildings," Berk said. "Now, we can come up with a logical approach to discovering how to take down their building, or prevent them from forming the building itself."

Combining super-resolution microscopy with the technique Berk developed, which allows continuous labeling of growing and dividing cells in culture, biologists in many fields will be able to record stop-motion video of "how bacteria build their castles," he said.

In a statement about the paper, Chu said, "Advances in single molecule methods based on optical microscopy have made stunning progress in the past two decades. In particular, 'super-resolution' imaging methods enabled researchers to image structures with unprecedented detail. Veysel Berk led a team that applied these optical methods to continuously image live biofilms on length scales on tens of nanometers to tens of microns. Before this work, these bacterial communities were largely studied in terms of their average composition, appearance and bulk biochemistry. By introducing a new in vivo fluorescence tagging strategy, the molecular and architectural roles of three specific matrix proteins and the extraracellular polysaccharides of a growing V. cholerae bioflim were visualized as series of three-dimensional images. This work has led to new insights into the development of these complex structures and will no doubt pave the way to new approaches to fighting infectious disease and also bacteriological applications in environmental and industrial settings."

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