In 2009, a mysterious fungus appeared seemingly out of thin air, targeting essentially the most vulnerable amongst us. It appears like Hollywood, however the fungus in query is a really real threat. Scientists try to work out what makes the deadly fungus tick — and why even one of the best infection control protocols in hospitals and other care settings often fail to eliminate it.
UM researchers zeroed in on its unusual ability to stick with the whole lot from skin to catheters and made a startling discovery.
The research team, led by Teresa O'Meara, Ph.D. The UM Medical School Department of Microbiology and Immunology and its graduate student Darren Santana discovered that it’s unlike another known fungus in that it uses a style of protein, called adhesin, that binds to marine organisms. Works like barnacles and mollusks.
Their original hypothesis was that one in all the adhesive protein families would use adhesins just like those utilized by other fungi. However, after they checked the same old suspects, namely proteins from the highly conserved ALS and IFF/HYR families, they turned out to be mostly short, apart from one protein, IFF4109, with a partial effect.
They then pointed to a distinct screening method to systematically break down the genome and see which mutants lost their ability to stick to 96-well plastic plates—leading to a A brand new adhesin was discovered, which they named surface colonization factor (SCF1).
“The new adhesin is only present in this one so we don't know where it came from evolutionarily. It doesn't seem to have come from any other organism by sequence similarity,” O'Meara said. They revealed that the bonds formed are cation-pi bonds, that are among the many strongest non-covalent chemical bonds in nature.
“Most of the literature about this type of bonding in nature comes from people trying to bioengineer glue that sticks underwater. So, they looked to nature for inspiration,” O'Meara said. Looked at.”
Additionally, the team discovered that SCF1 is related to increased colonization and enhanced disease-causing capability. Using mouse models, they demonstrated that lack of each SCF1 and IFF4109 reduced the flexibility of C. auris strains to colonize skin and indwelling catheters. Moreover, virulence and more fungal lesions were observed in strains engineered to overexpress SCF1.
“We don't know why this adhesin is needed to cause disease,” O'Meara said. “It may be that they need to attach to blood vessels, or they may change the host receptor interaction that is correct for the respective fungus, but we don't know in this case.”
O'Meara and his team plan to analyze the connection between SCF1 and the virus to take advantage of it for more practical antifungal therapy, as many strains are proof against existing drugs. O'Meara said the adhesin could also provide a clue as to where it got here from, with its barnacle-like adhesive properties suggesting a marine origin.
“Unlike SARS-CoV2, which emerged in one place, suddenly appeared in 5 separate locations around the world. There's some selective pressure in the world that changed that people were not colonized at risk.”
Additional authors include Darian J. Santana, Juliet AE Anku, Guolei Zhao, Robert Zarnowski, Chad J. Johnson, Haley Hautau, Noelle D. Visser, Ashraf S. Ibrahim, David Andes, Jeniel E. Nett, and Shakti Singh.