‘Off switch’ enzyme in biofilms identified to prevent formation
The switch that activates biofilm formation is a signaling molecule called Cyclic-di-GMP, also known as c-di-GMP.
E.coli, Salmonella enterica and Vibrio cholerae are among bacteria that use c-di-GMP to signal formation of biofilms.
The researchers said they are the first to identify the molecule that completes the process of clearing c-di-GMP from the cell, ending the biofilm signaling process.
The molecule is an enzyme called oligoribonuclease, and like c-di-GMP, it is also common among disease-causing bacterial species.
Impact on biofilm formation
Mona Orr, the lead author of the study and a UMD biological sciences graduate student, said the findings have broad implications for bacterial biofilms in general.
“The signaling molecule c-di-GMP is almost universally used by bacteria to increase biofilm formation,” she told FoodQualityNews.
“While we have known about this molecule for several decades, some aspects of how it was ultimately broken down remained a mystery. We found that this enzyme, oligoribonuclease, can complete the degradation pathway in P. aeruginosa.
“Since E. coli and S. enterica also both make oligoribonuclease, this enzyme likely performs the same role in their physiology.
“Depending on the types of organisms most commonly found in food factory contamination, they could also make use of this pathway.”
The team studied Pseudomonas aeruginosa, a common species known to cause infections in hospital patients.
But because of the genetic and physiological similarities between P. aeruginosa and other infectious species, they believe that oligoribonuclease serves the same function across a variety of bacteria.
Bacteria are best known as free-living single cells, but to survive in harsh environments, many species band together and form a biofilm—a collection of cells held together by a tough web of fibers that offers protection from different threats.
What researchers found
The team found that oligoribonuclease is necessary for the second of a two-step process.
The first, which converts c-di-GMP into an intermediate molecule called pGpG, was already known.
Researchers filled in the second step where oligoribonuclease breaks apart pGpG and shuts off the signaling pathway.
The result suggests oligoribonuclease could be used to help design new disinfectants, and surface treatments to control biofilms.
While oligoribonuclease most likely shuts down biofilm formation in many infectious bacterial species, the team acknowledged 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,” said 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.
“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.”
Orr said at this early point in the research, they have no drugs, disinfectants or treatment plans that could target or enhance this breakdown pathway to reduce biofilm formation.
“While this is not a "silver bullet" (and I would argue that a true silver bullet might never exist), better understanding of this widely-used biofilm-regulating molecule could lead to a more rapid development of biofilm removal options.”
The work was funded by the National Institutes of Health’s National Institute of Allergy and Infectious Diseases and the National Science Foundation.
Source: Proceedings of the National Academy of Sciences
Online ahead of print, DOI: 10.1073/pnas.1507245112
“Oligoribonuclease is the primary degradative enzyme for pGpG in Pseudomonas aeruginosa that is required for cyclic-di-GMP turnover”
Authors: Mona Orr, Gregory Donaldson, Geoffrey Severin, Jingxin Wang, Herman Sintim, Christopher Waters, and Vincent Lee
