U Researcher Tackles Drug Resistance in Pathogenic Fungi

University of Minnesota Medical School Department of Microbiology and Immunology’s Assistant Professor, Anna Selmecki, PhD, is a Dean's Fellow and a National Academy of Sciences’ Kavli Fellow. In addition to these accolades, she is an expert scientist and researcher on the topics of aneuploidy, genome stability, fungal pathogenesis and antifungal drug resistance. 

She started at Dana-Farber Cancer Institute and Harvard Medical School, where she completed her postdoctoral research and studied the phenomenon of polyploidy. She later moved to Omaha, Nebraska, to work as an assistant professor at Creighton University Medical School. There, she started her own lab studying the genomics of both budding yeast and the Candida species. 

Now in Minnesota, Dr. Selmecki said her choice to move back was easy, given that a thriving community of fungal and genomics researchers and her family live in the state. In December 2019, she received a research project grant (R01) from the National Institutes of Health for her proposal as the principal investigator to study “Aneuploidy and Acquired Antifungal Drug Resistance in Candida species.”

“It is exciting to be back here at the University of Minnesota and to be supported by this grant. This is a center for research and discovery in fungal pathogens in plants and humans, and it was a huge draw that led to me continuing my research here,” Dr. Selmecki said.

What is Candida?

According to the Centers for Disease Control and Prevention (CDC), Candida are species of yeast that normally live on our skin and inside the body without causing infections. However, overgrowth of Candida can cause fungal infections with symptoms ranging from mild oral thrush and vaginitis to life-threatening systemic infections. The ability to fight off these infections and the severity of the symptoms are often dependent on the strength of a patient's immune system.

More Candida species have become resistant to available antifungal medications, which makes treating fungal infections in patients increasingly difficult. The drug-resistant Candida species are listed on the CDC’s serious and urgent threat lists. Candida albicans is the most common fungal pathogen, but a new species, Candida auris, has quickly and seemingly without warning, become an urgent threat due to its inherent drug-resistance and ability to attach to surfaces and spread quickly in hospital settings.

Dr. Selmecki’s Study

“The rapid emergence of antifungal drug resistance in Candida species poses a serious antimicrobial threat worldwide,” Dr. Selmecki explained. “We have more treatment options for bacterial infections than we do for fungal infections, and my team is conducting experiments to determine how drug resistance occurs in Candida species in hopes of identifying new drug therapies.”

Dr. Selmecki and her team aim to identify the genomic mechanisms that allow these fungi to develop drug resistance. 

“We know that some genes in the genome are important for drug resistance, and our research continues to uncover new genes and mechanisms," Dr. Selmecki said. "For example, the copy number of these genes can change rapidly, and we think this is one mechanism that drives drug resistance. The same patterns occur in cancer cells, where they acquire copy number amplifications or deletions as they divide and grow."

She and her team of scientists are looking at the kinds of mutations that occur in Candida over time. Specifically, her team is comprehensively analyzing the mutations that occur in controlled evolution experiments in real time. They are also testing different combinations of available antifungal drugs. 

Dr. Selmecki notes that there are just a few antifungal therapies that are currently available for patients today. She draws an interesting parallel between how these organisms are in communication with other organisms in our bodies, such as bacteria and other fungi. The prevalence of antibacterial drugs now coursing throughout humankind could play a role in changing the balance of all microorganisms within us.

First thing’s first. 

There are two other aspects of this study. Dr. Selmecki and her lab are conducting a similarly controlled experiment, but in an animal model, observing mice that have been exposed to Candida. The third component of this study includes analyzing isolates obtained from patients that present with drug-resistant Candida. While these patient isolates are not from a controlled environment and are subject to many external factors, they do provide an understanding of the type and frequency of drug-resistant mutations occurring in clinical settings. 

Dr. Selmecki is proud of the team's continued bioinformatics research on understanding the structure and variability of Candida genomes, which was published recently in “eLife.” 

“Here at the University of Minnesota Medical School, I have access to many colleagues who are using bioinformatics and whole genome sequencing to address novel genomics-related questions,” Dr. Selmecki said. She and her team use the latest technology in the University’s Genomics Center, including the handheld MinION genomic sequencer from Oxford NanoPore Technology. The portability of the MinION allows scientists to take this device out into the field to test genomes in more remote locations. 

After Dr. Selmecki and her team have completed their experiments, they plan to use the findings to develop new therapies for patients to reduce the significant morbidity and mortality that is caused by diverse antifungal drug resistant Candida species.