This is the second in a two-part series that began last week on two scientists at Stony Brook Medical School who are working to unlock the secrets of different types of fungi that can cause significant health problems.
Like the cracks in the sidewalk that we don’t notice most of the time, Candida albicans is everywhere. Mostly, though, it’s on and around us. While this fungus is harmless much of the time, it has a dark side.
After prolonged catheterization (tubes entering the body) or in people with weakened immune systems, Candida can enter the bloodstream, where it can cause significant damage.
“It’s considered to be the fourth most commonly acquired hospital infection,” explained James Konopka, a professor in molecular genetics and microbiology at Stony Brook Medical School. It often targets the kidney. Even with current state-of-the-art antifungal drugs, Candida can become life threatening.
In most people, Candida often can’t get past the skin or the lining of the gastrointestinal tract. That, however, changes when, for example, patients have surgical procedures.
“A tube going into a patient can provide a site for a biofilm and can get it across the skin,” Konopka explained.
This can also be compounded, he explained, by the use of antibacterial drugs, which eliminate the bacteria and give the fungus more room to grow.
Patients with weakened immune systems, through AIDS, cancer treatments or immunosuppressive therapies, can also be the target of fungal infections.
Konopka is looking from the outside of Candida in, trying to alter the cell wall, or plasma membrane. Everything in the membrane is not randomly moving around, he explained. There are specialized sensors that can be instrumental in its life cycle.
He’s been studying genes that are responsible for 30 proteins in the membrane. He has deleted the genes for most of these proteins and plans to pick the best candidates for more study and drug development.
“If we disrupt the function of those proteins, that leads to a global defect in how the membrane is organized,” he said.
One of the challenges in fungal research is that humans and fungi are more closely related, evolutionarily, than humans and bacteria. On the positive side, that means research into basic cellular mechanisms of fungi may provide information about human cells.
On the downside, however, it provides a tricky type of Venn diagram for medical treatment. Doctors and researchers have to find drugs that only affect fungi and that don’t harm human cells at the same time.
The existing therapies have limitations. As with bacteria, some fungal strains have developed resistance.
Even finding a specific therapy that targets and eliminates Candida could lead to another unintended consequence. Because Candida lives within most of us without causing problems, eliminating all of the fungus could create an opening for an infection from another type of bacteria or fungus.
“There’s been some suggestion that that possibility may be occurring in certain patients in long-term drug therapy,” Konopka acknowledged.
He’s not convinced that’s the case, but it has caused some researchers to think Candida might be filling a niche that keeps worse invaders out.
The ideal therapy may involve a short-term treatment that clears Candida from internal organs, but resets the relationship to where the fungus lives within humans without doing any damage.
At the University of Washington in Seattle, Konopka had been doing basic fungal research under the guidance of Leland Hartwell, who shared the Nobel Prize in 2001 for discovering protein molecules that control the division of cells. When Konopka moved to Stony Brook, he transitioned to studying Candida.
In 2008, he discovered that deleting the proteins in the plasma membranes caused the cell wall to grow backwards.
“There’s a layer of regulation that keeps the cell wall on the inside,” he explained.
Konopka lives in East Setauket with his life, Susan Watanabe, a scientist who is studying HIV, the virus that causes AIDS.
He said he wades out into the water at West Meadow Beach, where he catches bluefish and striped bass.
As for working with fungus, there is an upside: yeast. In the fall, he hosts an Oktoberfest party for his entire building, where he and his guests sample each other’s home-brewed beer. Last fall, the offerings included Strong Island Ale, Rye Smile and Midnight Spice. Konopka provided Hoppy Oktoberfest, a beer he describes as a “classic,” which has “the taste of fresh grown hops, but brings with it a fair amount of sweetness.”