Fungal Threats

Increasing antifungal resistance in agricultural environments poses risks for human health

photomicrograph of Aspergillus fumigatus

This photomicrograph reveals a conidiophore that has branched from the hypha of an Aspergillus fumigatus fungal organism. (Image courtesy the Centers for Disease Control and Prevention)

This photomicrograph reveals a conidiophore that has branched from the hypha of an Aspergillus fumigatus fungal organism. (Image courtesy the Centers for Disease Control and Prevention)

While they may not have the shock factor of a high-budget Hollywood postapocalyptic tale, fungal infections are a growing threat to both agriculture and human health due to increasing antifungal medication resistance.

Research by University of Georgia scientists from the College of Agricultural and Environmental Sciences and the Franklin College of Arts and Sciences has shown, for the first time, that compounds used to fight fungal diseases in plants are causing resistance to antifungal medications used to treat people.

The study focused on Aspergillus fumigatus, the fungus that causes aspergillosis, a disease that causes life-threatening infections in 300,000 people globally each year. Published in G3: Genes, Genomes, Genetics, the study linked use of agricultural azoles — compounds used to fight fungal diseases in plants — to diminished effectiveness of the clinical azoles used to treat fungal infections in patients.

“Our results show that resistance to the compounds used to combat fungal infections in humans is developing in agricultural environments,” said Marin T. Brewer, a corresponding author of the study and the William Terrell Distinguished Professor in the CAES Department of Plant Pathology. “The samples that we collected in agricultural settings were resistant to both the azoles used in the environment and the clinical azoles used to treat people.”

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This medical illustration of azole-resistant fungus, Aspergillus fumigatus, was created for the Centers for Disease Control by a CAES alumnus.

Widespread danger

Fungi can be a menace for both people and plants, causing more than 1.5 million human deaths and crop losses of 20% annually.

It is not unusual to find A. fumigatus in the environment. It’s airborne, and it’s everywhere. Most people breathe it in without problem, but it can cause serious infections in people who have weakened immune systems.

When they’re infected by a strain of the fungus that’s resistant to agricultural azole fungicides, the clinical azole drugs used in health care are also ineffective.

“Azole-resistant A. fumigatus is widespread in agricultural environments and especially things like compost,” said Michelle Momany, a corresponding author of the study and a professor of fungal biology in the UGA Department of Plant Biology. “Someone who is immunocompromised and at risk for fungal infections should be very cautious in those settings.”

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Fungus strains on farms, in hospitals closely related

Brewer and Momany, both members of UGA’s interdisciplinary Fungal Biology Group, led a team that collected samples of soil, plant material and compost from 56 sites in Georgia and Florida. Most of the sites had recently been treated with a mix of fungicides including azoles and other fungicides that are only used in agriculture, not in patients. But two of the sites were organic and hadn’t used fungicides in more than a decade.

After recovering strains of A. fumigatus, the researchers found 12 that were highly resistant to azoles used in agriculture and medicine. The 12 strains also exhibited high levels of resistance to two non-azole fungicides that are not used to treat people.

The researchers used whole genome sequencing to create a genetic family tree for A. fumigatus strains from the environment and from patients. They found that the mechanisms of azole resistance they identified in the strains from agricultural environments matched what they saw in patients. The azole-resistant strains from patients were also resistant to the non-azole fungicides that are never used in people, showing that these strains had been in agricultural environments before the patients were infected.

“The strains that are from the environment and from people are very closely related to each other,” Brewer said. “It’s not like there are different strains that are developing resistance in people and in the environment. It’s all the same. So people who have these infections that are resistant have likely acquired them from the environment.”

Laxmi Pandey holds up a petri dish of moldy peanuts in a lab.

Laxmi Pandey, master’s student in Plant Pathology examines growth of seedborne peanut pathogens, including some Aspergillus species, in Marin Brewer’s mycology lab on March 21, 2023. (Photo by Katie Walker)

Laxmi Pandey, master’s student in Plant Pathology examines growth of seedborne peanut pathogens, including some Aspergillus species, in Marin Brewer’s mycology lab on March 21, 2023. (Photo by Katie Walker)

Petri dish of peanuts surrounded by circles of fungal growth
Stacks of petri dishes on a shelf

Lab samples grow in a humidifer in Marin Brewer's mycology lab.

Lab samples grow in a humidifer in Marin Brewer's mycology lab.

Sample vials lined up in a humidifier with Marin Brewer's face reflected in the glass over the samples

Marin Brewer's face is reflected in the glass door of a humidifer in her lab. Brewer researches fungal pathogens such as Aspergillis species in the Miller Plant Sciences building on the University of Georgia's Athens campus on March 21, 2023.

Marin Brewer's face is reflected in the glass door of a humidifer in her lab. Brewer researches fungal pathogens such as Aspergillis species in the Miller Plant Sciences building on the University of Georgia's Athens campus on March 21, 2023.

Aspergillus fungal spores
Natalie Miller and Christian Ona work beside Marin Brewer in her lab.

Student researchers work in Marin Brewer's plant pathology lab in the Miller Plant Sciences building on the University of Georgia's Athens campus on March 21, 2023. From left to right, undergraduate students Natalie Miller and Christian Ona prepare samples with Brewer.

Student researchers work in Marin Brewer's plant pathology lab in the Miller Plant Sciences building on the University of Georgia's Athens campus on March 21, 2023. From left to right, undergraduate students Natalie Miller and Christian Ona prepare samples with Brewer.

A desperate need

Of the 25 multiazole-resistant strains included in the study, eight from agricultural environments and 12 from patients were also resistant to the non-azole agricultural fungicides when compared to publicly available whole genome sequences of strains gathered during previous studies. These multifungicide-resistant strains were from agricultural settings in the U.S. and India and clinical settings in the U.S., the Netherlands and India.

“This emergence severely limits the usefulness of fungicides to manage plant pathogens while still preserving the clinical usefulness of azoles,” Brewer said. “We urgently need effective agricultural fungicides that aren’t toxic to the environment and do not lead to the development of widespread resistance in the clinic.”

The research was funded by the U.S. Centers for Disease Control and Prevention and UGA’s Presidential Interdisciplinary Seed Grant program.

Co-authors include Brandon Mangum, a graduate student in the Department of Plant Biology, and former UGA students S. Earl Kang, currently at Ginkgo Bioworks; Tina Melie, currently at the University of Colorado; and Leilani G. Sumabat, currently at the University of the Philippines Diliman.

Portrait photo of Stephanie Rossow

Rossow created the illustration of Aspergillus fumigatus in the story above.

Rossow created the illustration of Aspergillus fumigatus in the story above.

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About the Illustrator

Vector Vision

Animal science grad works as scientific illustrator for CDC

By Anna Bentley

Stephanie Pfeiffer Rossow has played a major role in depicting some of the world’s most notorious bacteria, viruses and fungi, including those that cause COVID-19 and mpox.

A graphic artist for the Centers for Disease Control and Prevention’s (CDC) Visual Design Branch, Rossow partners with researchers and health communications specialists across all CDC centers to help tell stories with vital global significance. Through a contract with Peraton Corporation, her team helps disparate audiences make sense of emerging diseases, chronic conditions and localized outbreaks through clear, accurate and engaging illustrations.

Since joining Peraton in 2018, Rossow, a 2013 animal science graduate from the University of Georgia’s College of Agricultural and Environmental Sciences, has also helped the CDC execute cohesive emergency response campaigns for a cholera outbreak in Haiti, Ebola outbreaks in the Democratic Republic of Congo and hurricanes in Puerto Rico. 

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“What I love is that we’re able to support the CDC mission,” Rossow said, “We’re able to take part in having that larger impact on the health of the nation and the world through getting public health communications out there — I know that each piece of artwork that I create has a purpose and will affect people’s lives.”

Medical illustration is a natural fit for Rossow, who grew up with a love of art and an inclination toward science — “I’ve always been between the two worlds,” she explained. She pursued both interests at UGA, completing the undergraduate coursework necessary for veterinary school while earning a minor in studio art. She discovered scientific illustration through her art courses, and a postgraduate job illustrating for the UGA College of Veterinary Medicine solidified a career in medical illustration, a seemingly tailor-made niche where she could elucidate the sciences through art.

“The field is an interesting intersection between art and science. I think that was what personally drew me into combining the love of being an artist and designer, having that creative outlet, with the communication purpose and education purpose,” she said.

Illustrating for public health communications requires critical consideration of the art and the message, both carefully tailored to the intended audience. Rossow harnesses her understanding of the impact of color, typeface, illustration style and word choice on how the audience receives a message. An article for children about the common cold may feature brighter colors and a cartoonish style, for example, while a laboratory research update for health professionals may call for highly realistic illustrations and precise terminology. 

Rossow’s team helps bring to life abstract concepts like the social determinants of health as well as microscopic organisms and disease transmission. The design process is an exercise in creative translation from hard science to easily decodable illustration. It is also highly collaborative — through all phases of design and development, Rossow cooperates closely with CDC researchers and subject matter experts to ensure that her team’s illustrations are accurate and effective.

“That’s what’s so fascinating about this career field,” she said. “You get a new project, and you get to work with the top experts in the field and learn all about a specific disease or condition and the research that’s out there. You get to learn something new every time.”

pill-shaped Shigella bacteria with cilia

Rossow illustrated this image of drug-resistant Shigella sp. bacteria.

Rossow illustrated this image of drug-resistant Shigella sp. bacteria.

Histoplasma fungal spores

Histoplasma

Histoplasma

Candida auris fungal spores

Candida auris 

Candida auris 

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