The battle lines have finally shifted in the war against a deadly fungal disease.
The fungal pathogen Aspergillus fumigatus has long been known to cause a severe, rapid respiratory infection, and it has become harder to fight.
"Even with treatment, the mortality rate can vary between 30-90 percent," said José M. Vargas-Muñiz, assistant professor of biological sciences . "And now environmentally acquired antifungal-resistant Aspergillus are starting to infect patients."
Vargas-Muñiz, an affiliate with the Center for Emerging Zoonotic and Arthropod-borne Pathogens , was recently a part of a team of researchers who have added a new strategy to the battle. Led by Rebecca Jean Busch, Ph.D. candidate in biological sciences, they successfully killed the fungal pathogen in animal studies by identifying how it resists current therapeutic methods.
Published in Molecular Biology of the Cell , the researchers believe this could be the key to defeating the fungus.
Researchers Rebecca Busch and José Vargas-Muñiz successfully killed the fungal pathogen Aspergillus fumigatus in their study, which may help lead to improved therapeutic treatments in the future. Photo by Felicia Spencer for Virginia Tech.
"It lays the groundwork for the future," Busch said. "There's a lot of people who just don't know that these terrible fungal diseases exist. This is different; it's an invasive fungal infection and hard to diagnose unless the doctors already kind of know what they're looking for."
According to the authors, this pathogen has the highest per patient cost of any invasive fungal disease, costing the United States an estimated $1.3 billion per year.
Like other airborne pathogens, inhaling fungal spores in the environment is how one becomes infected, much like how one becomes infected with other aerosolized pathogens such as hantavirus, influenza, or tuberculosis, according to Vargas-Muñiz, also affiliated with the Fralin Life Sciences Institute .
People with healthy immune systems easily combat the pathogen, but those who are immunocompromised do not. Busch said this is often compounded by the prevalence of drugs used to treat psoriasis or rheumatoid arthritis, which can cause patients, unknowingly, to be immunocompromised.
The frontline treatment, the triazole class of drugs, can kill the pathogen, but, because they are chemically similar to those used as agriculture fungicides, sometimes they don't. The second line of treatment drugs, echinocandins, do not kill the pathogen; they stop the growth of the fungus but they do not kill it.
"When it comes to antifungal drugs, there are very few options available compared to antibacterial drugs. We have hundreds of antibacterial drugs, and we have somewhere around 10 [antifungal drugs]," Busch said. "Once you get a strain of the fungus that's resistant, it's like, what else do we treat you with?"
With a goal of helping to improve the efficacy of the antifungal drugs, the researchers set out to better understand the mechanism that renders the echinocandins essentially ineffective.
Because the echinocandin drugs attack the fungal cell wall, Busch's team genetically modified the fungal pathogen by stripping it of the proteins that regulate cell walls to identify which are integral to the pathogen's defenses.
In both lab and animal tests, this allowed the echinocandin drug to kill the genetically modified pathogen. This success proves the means by which the proteins prevent the drug from currently killing the pathogen, and it better identifies which protein is most responsible.
Having identified the weakness in their fungal opponent, the researchers are now strategizing for more targeted attacks with the echinocandins.
Other researchers involved with this study include the following:
- Tatiana Boluarte, research associate, biological sciences, Virginia Tech
- Francisco Carvallo, clinical professor, biomedical sciences and pathobiology, Virginia-Maryland College of Veterinary Medicine at Virginia Tech
- Carson Doty, undergraduate student, biological sciences, Southern Illinois University-Carbondale
- Laura E. Herring, associate professor, Michael Hooker Metabolomics and Proteomics Core Facility, University of North Carolina at Chapel Hill
- Vjollca Konjufca, professor, microbiology, Southern Illinois University-Carbondale
- Flutur Latifi, M.D., Ph.D. candidate, microbiology, Southern Illinois University-Carbondale
- C. Allie Mills, Ph.D., Michael Hooker Metabolomics and Proteomics Core Facility, University of North Carolina at Chapel Hill
