Solving a sticky, life-threatening problem

Researchers at U-M have zeroed in onC. auris'uncanny ability to stick to everything from skin to catheters and made a startling discovery.

The investigative team, led by Teresa O'Meara, Ph.D. of the U-M Medical School Department of Microbiology and Immunology and her graduate student Darian Santana, has discovered thatC. aurisis unlike any other known fungus in that it employs a type of protein, called an adhesin, that acts very similar to those used by oceanic organisms, such as barnacles and mollusks.

Their original hypothesis was thatC. auriswould use an adhesin from the families of sticky proteins used by other fungi likeC. albicans．然而,当他们检查通常的嫌疑人,namely proteins from the highly conserved ALS and IFF/HYR families, they came up mostly short, except for one protein, IFF4109, with a partial affect.

They then pivoted to a different screening method to systematically break the genome ofC. aurisand see which mutant lost its ability to stick to 96-well plastic plates -- leading to the discovery of a new adhesin they named Surface Colonization Factor (SCF1).

"The new adhesin is only present inC. aurisso we don't know where it came from evolutionarily. It doesn't look like it came from any other organisms by sequence similarity," said O'Meara. The bonds formed byScf1, they revealed, are cation-pi bonds, which are among the strongest non-covalent chemical bonds in nature.

Said O'Meara, "Much of the literature about this type of bond in nature comes from people trying to bioengineer glue that adheres underwater. Hence, they've looked to nature for inspiration."

Furthermore, the team discovered that SCF1 was associated with increased colonization and an enhanced ability to cause disease. Using mouse models, they demonstrated that a loss of both SCF1 and IFF4109 diminished the ability of a strain of C. auris to colonize skin and an in-dwelling catheter. What's more, strains designed to over express SCF1 saw enhanced virulence and more fungal lesions.

"We don't know why this adhesin is required to cause disease," said O'Meara. "It could be that they're required to attached to blood vessels, or maybe they change the host-receptor interactions which has been true for the related fungusCandida albicans, but we don't know in this case."

O'Meara and her team plan to investigate the link between SCF1 and virulence in the hopes of exploiting it for a more effective anti-fungal therapy, as many strains ofC. aurisare resistant to current medications. The adhesin may also provide a clue about whereC. auriscame from, said O'Meara, with its barnacle-like adhesive properties suggesting an oceanic origin.

"Unlike SARS-CoV2, which emerged in one place,C. auris突然出现在5 t截然不同的地方he world. There's some selective pressure in the world that changed that allowedC. auristo go from not a threat at all to colonizing people."

Additional authors include Darian J. Santana, Juliet A. E. Anku, Guolei Zhao, Robert Zarnowski, Chad J. Johnson, Haley Hautau, Noelle D. Visser, Ashraf S. Ibrahim, David Andes , Jeniel E. Nett , and Shakti Singh