Bacteria, which most of us think of as free-living single cells, in reality live much more complex lives. In order to survive in harsh environments, many species of bacteria will join together and form a biofilm.
Biofilms are a collection of cells held together by a tough web of fibers. It offers protection from all manner of threats, including antibiotics. One familiar biofilm is the dental plaque that forms on teeth between brushings.
But biofilms can form almost anywhere given the right conditions.
In the health care industry, Biofilms are a big problem. When disease-causing bacteria establish a biofilm on sensitive equipment, it can be impossible to sterilize the devices, raising rates of infection and necessitating expensive replacements.
So researchers search for ways to break down the defenses of biofilms to prevent them from establishing a foothold.
Now, a University of Maryland-led team has found an important link in the biofilm formation process.
They identified an enzyme that shuts down the signals that bacteria use to form a biofilm. The findings have far-reaching implications for the development of new treatments, and could one day help turn biofilm-related complications into a fading memory.
Lead author Mona Orr, a UMD biological sciences graduate student, said:
“Bacteria form biofilms because they sense a change in their environment. They do this by generating a signaling molecule, which binds to a receptor that turns on the response.
But you need a way to turn off the switch—to remove the signal when it’s no longer needed. We’ve identified the enzyme that completes the process of turning off the switch.”
The well-known switch that activates biofilm formation is a signaling molecule called Cyclic-di-GMP, also known as c-di-GMP. Many species of disease-causing bacteria use c-di-GMP to signal the formation of biofilms, including Escherichia coli, Salmonella enterica and Vibrio cholerae.
But Orr and her colleagues are the first to identify the molecule that completes the process of clearing c-di-GMP from the cell, thus ending the biofilm signaling process. The molecule is an enzyme called oligoribonuclease, and much like c-di-GMP, oligoribonuclease is also common among disease-causing bacterial species.
Filling the Sink
Vincent Lee, a co-author of the study and an associate professor in the UMD Department of Cell Biology and Molecular Genetics and the Maryland Pathogen Research Institute, said:
“You can think of this process in terms of water filling a sink. The rate of water from the faucet is just as important as the size of the drain in determining the level of water in the sink.
The level of c-di-GMP in the cell is analogous to the amount of water in the sink. Because no one knew what the drain was, our findings create a complete picture of the signaling process.”
While oligoribonuclease most likely shuts down biofilm formation in many infectious bacterial species, Orr and Lee acknowledge that their discovery is not quite a “silver bullet” that can fight every type of biofilm.
“The genes that make these signals are found in most bacteria. The oligoribonuclease enzyme that breaks the effect is only found in some, however,” Lee explained. “So there must be parallels in the organisms that don’t have oligoribonuclease. Finding these other ‘off’ switches is high on our list of future research goals.”
Mona W. Orr, Gregory P. Donaldson, Geoffrey B. Severin, Jingxin Wang, Herman O. Sintim, Christopher M. Waters, and Vincent T. Lee
Oligoribonuclease is the primary degradative enzyme for pGpG in Pseudomonas aeruginosa that is required for cyclic-di-GMP turnover
PNAS 2015; doi:10.1073/pnas.1507245112
Illustration: In this false-colored image, individual cells of Pseudomonas aeruginosa (green) can be seen resting on the fibrous surface of a biofilm (purple) that helps protect cells beneath its surface. At top right, two cells incorporated within the biofilm peek out from a fissure in the film’s surface. Credit: Debra Weinstein, Sao-Mai Nguyen-Mau, and Vincent Lee