McMaster University researcher Lindsay Kalan (right) and MSc student Jordana Ferro examine a dish containing skin-associated bacteria.
Photo Credit: Courtesy of McMaster University
Scientific Frontline: Extended "At a Glance" Summary: The Skin Microbiome as an Antimicrobial Reservoir
The Core Concept: The human skin microbiome constitutes a vast, diverse community of bacteria, fungi, and viruses that acts as a protective barrier against external pathogens. Recent research indicates that these endogenous microbial populations naturally produce novel antimicrobial compounds to defend their host.
Key Distinction/Mechanism: Unlike traditional antibiotic discovery, which typically relies on isolating microbes from environmental soil samples, this framework investigates the human body's native flora. Certain newly discovered skin-associated bacterial species act as "fungal specialists," synthesizing previously uncharacterized chemical molecules to directly inhibit drug-resistant pathogens.
Major Frameworks/Components:
- Epithelial Isolate Collection (EPIC): A comprehensive microbial library gathered from eight distinct microenvironments on the human body, representing an estimated 95 percent of the entire human skin microbiome.
- Biosynthetic Gene Clusters: Genetic sequences responsible for producing antimicrobial chemicals. Analysis revealed that 96 percent of the identified clusters in these specific skin microbes remain uncharacterized, suggesting immense potential for novel molecular discovery.
- Fungal Specialists: Three of the newly discovered bacterial species demonstrate a highly effective ability to deter severe, drug-resistant fungal pathogens, including Candida auris and species within the Cryptococcus genus.
- Broad-Spectrum Defense: Validation experiments confirmed that these skin microbes possess chemical defenses active against over 20 human pathogens, including Escherichia coli and Staphylococcus aureus.
Branch of Science: Microbiology, Biochemistry, Biomedical Sciences, and Infectious Disease Pharmacology.
Future Application: The extraction and synthesis of novel clinical antibiotics, the development of targeted antifungal treatments, and the engineering of live skin probiotics designed to continuously harness host-defense bacteria.
Why It Matters: With antimicrobial resistance posing an escalating global health crisis, the human skin microbiome presents a massive, untapped reservoir of novel chemistry, offering urgent therapeutic solutions to combat multidrug-resistant infections.
The answer to one of medicine’s most urgent challenges—the search for new antibiotics and other antimicrobials—may be hiding in an unexpected place: the bacteria living on our own skin.
From head to toe, the human body is crawling with beneficial microbes—bustling communities of bacteria, fungi, and viruses that exist all across our skin. Together, these communities make up a vast microbial metropolis called the skin microbiome, which acts as a protective barrier that helps shield us from other, more dangerous microbes.
In a new study out of McMaster University, researchers have shed light on how the skin microbiome protects human health, and their findings suggest that our own skin could be an untapped reservoir of new antibiotics and other antimicrobial chemicals.
Published today in the journal Nature Communications, the new study involved more than thirty volunteers who were swabbed at eight different body sites representing distinct microenvironments, including the neck, outer nose, nostrils, back, arms, forearms, belly button, and toes.
Together, the swabs pulled in 968 unique strains of bacteria—including four previously undiscovered species—to help establish the largest and most diverse collection of skin-associated microbes ever assembled.
Lindsay Kalan, an associate professor in McMaster’s Department of Biochemistry and Biomedical Sciences and principal investigator on the new study, estimates that the new library—dubbed the Epithelial Isolate Collection, or “EPIC”—represents 95 percent of the entire human skin microbiome.
Kalan says that the ambitious research project, which was featured by Nature Communications as an Editor’s Highlight, was inspired by a growing body of evidence that suggests microbes play a critical role in protecting animal health, pointing to recent discoveries made by McMaster researchers Cameron Currie and Jianping Xu. Currie discovered that leaf-cutting ants harbor symbiotic bacteria to defend their food source from infection, and Xu discovered that the bacteria found on bat wings may prevent a highly fatal fungal disease called white-nose syndrome.
“We looked at the human microbiome the same way,” says Kalan, associate director of McMaster’s Michael G. DeGroote Institute for Infectious Disease Research. “We isolated samples from the gut, the nose, the mouth, and the skin, and found that the skin microbiome exerted a remarkable amount of antimicrobial activity.”
Kalan’s group validated its early findings by systematically exposing the new library of skin-associated bacteria to a broad panel of more than twenty human pathogens, ranging from bacteria like Escherichia coli and Staphylococcus aureus to fungi like Cryptococcus and multidrug-resistant Candida auris. These experiments revealed that many members of the skin microbiome produced an array of antimicrobial chemicals capable of warding off invaders.
Researchers then zeroed in on the four new species of bacteria uncovered by their skin swabs and found that three of them produced chemicals that were especially effective at deterring disease-causing fungi.
“These new species of bacteria are what we’re calling ‘fungal specialists,’” Kalan says. “They can inhibit several different kinds of pathogenic fungi, including those that are otherwise drug-resistant.”
The team’s next challenge was determining whether these newly discovered microbes were producing new chemistry or if they were recycling previously discovered molecules produced by other known bacteria.
“What we found was a tremendous amount of novelty,” Kalan says.
In fact, across all of the skin bacteria studied, researchers found that only 4 percent of the gene clusters traditionally responsible for antimicrobial production had been previously characterized, suggesting the remaining 96 percent could encode potentially new molecules.
“This work shows that the human skin microbiome is a rich source of new molecules, many of which could have important clinical applications,” says Kalan. “This new collection of skin-associated bacteria presents us with a huge opportunity to explore a ton of new chemistry.”
Kalan’s team is now working to better understand the medicinal potential of the most intriguing new molecules while also exploring whether the producing bacteria themselves could one day be harnessed as skin probiotics.
Funding: This work was supported in part by the National Institutes of Health, the Weston Family Foundation, and the Canada Research Chairs Program.
Published in journal: Nature Communications
Authors: Uyen Thy Nguyen, Rauf Salamzade, Shelby Sandstrom, Mary Hannah Swaney, Elizabeth C. Townsend, Sherrie Y. Wu, J. Z. Alex Cheong, Joseph A. Sardina, Isabelle Ludwikoski, Mackinnley Rybolt, Hanxiao Wan, Caitlin M. Carlson, Jordana Ferro, Owen McArthur, Won Se Suh, Robert Zarnowski, David R. Andes, Cameron R. Currie, and Lindsay R. Kalan
Source/Credit: McMaster University | Blake Dillon
Edited by: Scientific Frontline
Reference Number: mcb072126_01
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