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Discovery of Antimicrobial Molecule from Skin Fungus
Researchers at the University of Oregon have identified a molecule produced by yeast residing on human skin, which exhibits strong antimicrobial properties against Staphylococcus aureus—a pathogen linked to approximately 500,000 hospitalizations in the U.S. each year.
This innovative research could provide a novel avenue for addressing the escalating issue of antibiotic-resistant bacteria. Caitlin Kowalski, a postdoctoral researcher involved in the study, emphasizes the potential of skin fungi to serve as a valuable source in the search for new antibiotics.
The findings were detailed in a paper published in Current Biology, highlighting the common skin fungus Malassezia’s ability to metabolize oils and fats from human skin, producing fatty acids that effectively target Staphylococcus aureus. While this bacterium typically exists harmlessly in the nasal passages of about one-third of the population, it poses a significant danger when there are breaks in the skin’s barrier, leading to infections known as staph infections.
Staphylococcus aureus also stands out as a notorious hospital-acquired superbug resistant to many existing antibiotics, underscoring the urgent need for new treatment options.
Kowalski noted, “While numerous studies uncover new antibiotic structures, what makes ours particularly intriguing is that we identified a compound that has been documented and studied before.”
This compound demonstrates non-toxic characteristics under standard laboratory conditions but exhibits considerable efficacy in an environment mimicking the acidic conditions prevalent on healthy skin.
“We may have previously overlooked these antimicrobial mechanisms due to higher pH levels in laboratory settings,” Kowalski explained, adding that human skin typically has a more acidic pH.
The human body hosts a diverse array of microorganisms known collectively as the microbiome; however, limited research has focused on the role of resident fungi in human health. According to Kowalski, the skin microbiome is particularly noteworthy because it is primarily dominated by the Malassezia genus, unlike other body areas where multiple fungal species coexist.
While Malassezia can be linked to conditions like dandruff and eczema, it is generally considered a benign and standard component of skin flora. The yeast has adapted to thrive on mammalian skin, relying on the lipids produced by the skin for synthesizing fatty acids.
Kowalski remarked on the underexploitation of Malassezia despite its prevalence: “The skin’s microbiome is akin to what we observe in the gut, which has received much attention. We know that microbes in the gut can modify host compounds and create unique substances with newfound functions. The skin, being lipid-rich, also processes these lipids to produce bioactive compounds. This prompts questions about its implications for skin health and related diseases.”
Through analysis of skin samples from healthy individuals and laboratory experiments with skin cells, Kowalski discovered that Malassezia sympodialis converts host lipids into antibacterial hydroxy fatty acids. These fatty acids not only serve as essential building blocks for cell membranes but also possess significant antimicrobial effects.
The hydroxy fatty acids produced by Malassezia sympodialis exhibited detergent-like properties, disrupting the cellular membranes of Staphylococcus aureus and leading to the leakage of its cellular contents. This process effectively hindered the colonization of the bacteria on skin and could eliminate the bacteria within just 15 minutes, as noted by Kowalski.
However, the fungus is not a universal solution. Prolonged exposure can lead to bacterial tolerance, similar to patterns observed with the overuse of clinical antibiotics.
In their genetic analysis, researchers identified a mutation in the Rel gene of the bacteria, which activates stress responses. Such mutations have been previously observed in patients suffering from Staphylococcus aureus infections.
This research illustrates how a bacterium’s living environment and its interactions with other microorganisms can significantly impact its resilience to antibiotics.
Kowalski remarked, “There is growing interest in using microbes therapeutically, such as introducing specific bacteria to inhibit pathogen growth. However, the ramifications of such approaches are not completely understood. While we acknowledge that antibiotics can drive the evolution of resistance, this consideration is often overlooked in the application of microbes as therapeutic agents.”
Despite the complexities introduced by these findings, Kowalski remains optimistic about the potential of fungi on human skin to yield new antibiotic compounds.
The identification of these antimicrobial fatty acids was the result of three years of interdisciplinary collaboration. Kowalski worked alongside chemical microbiologists at McMaster University to isolate the compound.
“It was akin to locating a needle in a haystack, albeit with invisible molecules,” remarked Matthew Barber, Kowalski’s advisor and an associate professor of biology at the UO.
Kowalski is pursuing a follow-up study aimed at delving deeper into the genetic mechanisms that facilitate antibiotic tolerance. She plans to establish her own lab to further explore the frequently overlooked role of the skin microbiome after transitioning from Barber’s lab.
“Antibiotic-resistant bacterial infections pose a significant health threat that continues to escalate,” Barber concluded. “We have much to uncover about these microorganisms and about discovering new avenues for potential treatments or preventive measures against these infections.”
More information: Caitlin H. Kowalski et al, Skin mycobiota-mediated antagonism against Staphylococcus aureus through a modified fatty acid, Current Biology (2025). DOI: 10.1016/j.cub.2025.03.055
Source
phys.org