We often think of bacteria as a group of rapidly proliferating, free-living cells that don’t typically unite toward a common purpose. However, this couldn’t be further from reality, as microbial existence is much more complex than many may envision. For instance, a number of bacterial species often band together into a collection of cells held tightly together by a tough web of fibers, commonly known as a biofilm. A biofilm is any group of microorganisms in which cells stick to each other on a surface. These adherent cells are frequently embedded within a self-produced matrix of extracellular polymeric substance). This microbial unification affords the bacteria protection from outward threats such as antibiotics. By way of example, dental plaque, which forms on teeth in between brushings, is the biofilm familiar to most.
In recent years, biofilms have come into the spotlight due to their resistance to common disinfectant protocols—a particular cause for concern within the healthcare industry. In many cases, it becomes impossible to sterilize medical equipment, raising infection rates and necessitating expensive replacements. Consequently, scientists have been on the hunt for ways to prevent biofilms from establishing a foothold.
Now, researchers from the University of Maryland (UMD) believe they have found an important part of the biofilm formation process—the enzyme that shuts down the signals bacteria use to form a biofilm.
“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,” explained lead author Mona Orr, a UMD biological sciences graduate student. “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 findings from this study were published recently in PNAS through an article entitled “Oligoribonuclease is the primary degradative enzyme for pGpG in Pseudomonas aeruginosa that is required for cyclic-di-GMP turnover.”
It had been established previously that the signaling molecule Cyclic-di-GMP (c-di-GMP) was the switch that activates the biofilm formation process in many bacterial species. The UMD researchers, however, identified the molecule that completes the process of clearing c-di-GMP and ceasing the biofilm process. The molecule is an enzyme called oligoribonuclease, and much like c-di-GMP, oligoribonuclease is also common among disease-causing bacterial species.
The investigators studied the process in the bacteria Pseudomonas aeruginosa, a common species known to cause infections in hospital patients. Yet, due to the genetic and physiological similarities between P. aeruginosa and other infectious species, the researchers believe that oligoribonuclease serves the same function across a wide variety of bacteria.
“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,” said co-author Vincent Lee, Ph.D., associate professor in the UMD Department of Cell Biology and Molecular Genetics and the Maryland Pathogen Research Institute. “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.”
The team found that oligoribonuclease is necessary for the second of a two-step process. The first, converts c-di-GMP into an intermediate molecule called pGpG, then oligoribonuclease breaks apart pGpG and thus completely shuts off the signaling pathway.
The results from the current study suggest that oligoribonuclease could be used to help design new antibiotics, disinfectants, and surface treatments to control biofilms.
“The genes that make these signals are found in most bacteria. The oligoribonuclease enzyme that breaks the effect is only found in some, however,” Dr. Lee noted. “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.”