On the Hunt for New Strategies to Defeat a Killer Fungus

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Michael Mansour, MD, PhD

At first glance, Candida auris (C. auris) seems like the fungus equivalent of a comic book supervillain—at least from a human perspective.

A new species of infectious fungus that arrived seemingly out of nowhere a decade ago, C. auris is resistant to all known forms of antifungal drugs, and it sticks to surfaces so well that it resists standard hospital decontamination procedures.

Outbreaks of C. auris infections have shut down major surgery centers and care units with more than a third of the cases resulting in fatalities per the Centers for Disease Control.

Michael Mansour, MD, PhD, an Infectious Disease specialist focusing on fungal pathogens at Massachusetts General Hospital, is helping to lead efforts at the hospital to better prepare for C. auris outbreaks and identify new drugs and treatment strategies to fight back.

It’s an effort that blends his clinical work treating patients with severe fungal infections with his laboratory research examining how harmful fungal species can survive and thrive in the body.

C. auris is here and it doesn’t appear to be going away,” Mansour says. “Many other hospitals are dealing with it in high volume, so it’s something we need to learn to prepare for.”

A threat emerges

Candida is a type of fungus, that naturally exists in the human body. Many of the species are harmless, often causing diaper rash in children or vaginal yeast infections in otherwise healthy individuals.

If the immune system is functioning well, these infections are not usually serious. However, in patients who have had their immune systems suppressed as part of cancer treatment or an organ transplant, invasive Candida infections can be life-threatening.

Candida auris is the newest—and perhaps most harmful—species of Candida yet to be identified.

“The twist was not just that it was a new species, but that it was also incredibly resistant to many of the current antifungal drugs,” Mansour explains. “Some other species show resistance, but not like Candida auris. We’ve always had at least one drug that still works. Right off the bat, we found it alarming that there were so few options with which to treat patients.”

“The other big issue is that C. auris sticks to surfaces very well, so routine decontamination procedures were ineffective,” Mansour says. “A patient would be identified as having an C. aurisinfection. After discharge and routine cleaning, we thought the room was sanitized. But to our surprise, it wasn’t. C. auris could still be identified.”

For that reason, many hospitals had to temporarily shut down large surgical and clinical programs because they couldn’t stop C. auris outbreaks from spreading among patients.

C. auris infections have been reported in many parts of the world, from Japan to South Korea, India, the Middle East, Europe and the United States. Mass General was the first hospital in Massachusetts to discover and report a case of C. auris, which occurred in a lung transplant patient.

Preparing a response

Mansour is part of a larger effort within the Division of Infectious Diseases, Infection Control, and the microbiology laboratory at Mass General to prepare the hospital’s response strategy to new C. auriscases.

“We have a system in place that I’m confident will allow us to identify C. auris quickly. We have adopted new regulations that would activate a series of investigations to track potential exposures, change how we care for that patient and decontaminate afterwards.”

In his laboratory work, Mansour and his team are studying C. auris samples to identify potential weaknesses that can be targeted with new drugs or therapeutic strategies.

“My lab has developed interesting evidence for new classes of antifungal drugs. Under strict safety precautions, we grow C. auris in the lab for testing against these new agents and we’re getting good results,” he says.

While this progress is encouraging, Mansour cautions that there will still be years of research and development work before the drugs are approved for treatment. New partnerships with industry could help to move that process along.

“We’ve filed for patent applications on these antifungals. We’ve made it attractive to industry partners if they have interest in developing a novel class of antifungal drugs.”

Moving forward

In addition to tackling this new threat, Mansour is working to better understand the factors that contribute to fungal infections in immunocompromised patients.

“As a physician-scientist, my laboratory is conducting projects where patient samples are analyzed in the lab. We’re trying to understand why one transplant patient develops a fungal infection, but not the transplant patient next door.”

“If I know up front that a patient is at high risk, I can manage their care differently to reduce the likelihood they will suffer from an invasive fungal infection.”

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