Researchers at Baylor College of Medicine, along with international collaborators, have identified new factors that allow the fungus Candida albicans to colonize and persist in the gut. Their findings were published in Microbiology Spectrum.
Candida albicans is present in the guts of about 80% of people. While it often remains harmless, it can sometimes cause serious infections affecting organs such as the urinary tract, lungs, and brain. Understanding how this fungus establishes itself in the gut may help prevent these harmful infections.
“Our study revealed unexpected findings,” said first author Kelsey Mauk, a graduate student in the lab of Dr. David Corry at Baylor. “Most previous studies were conducted in mice that had been treated with antibiotics or drugs to suppress the immune system before introducing C. albicans. The assumption was that infection would not be possible without those treatments.”
Mauk and colleagues examined how C. albicans colonizes the gut under normal conditions without antibiotic or immunosuppressive treatment. They found that a clinical strain called CLCA10 could remain in the mouse gut for at least 58 days without causing weight loss, inflammation, or changes to bacterial populations in the gut. Treatment with antifungal medication reduced but did not eliminate fungal presence.
The study also found that C. albicans mostly remained within the contents and mucus layer of the gut. Other human-associated fungal species did not establish themselves under similar conditions.
The researchers tested whether host-related factors like sex, diet, or commercial source influenced colonization by C. albicans but found no effect from any of these variables.
“It turned out that none of these factors affected the ability of the fungus to establish itself in the gut,” Mauk said. “C. albicans can make itself at home under many different conditions.”
They also looked into fungal-specific factors thought to influence colonization, focusing on candidalysin—a peptide toxin produced by C. albicans hyphae known for its role in virulence—as well as two other proteins: adhesins Als3 and Hwp1.
“We thought that candidalysin would not contribute to C. albicans colonization because it triggers strong responses in the gut,” Mauk said. “The experiments blew away our expectations. It turned out that candidalysin as well as two other hypha-associated proteins – adhesins Als3 and Hwp1– were necessary for the fungus to take root and persist in the gut. Mice infected with strains lacking these proteins had much lower levels of fungal colonization.”
“This study shows that C. albicans gut colonization in the mouse is critically dependent on fungal hyphal factors,” said Corry, Fulbright Endowed Chair in Pathology, Immunology and Medicine and member of the Dan L Duncan Comprehensive Cancer Center at Baylor. “Therapeutically targeting these factors could enhance strategies to reduce C. albicans gut colonization and the intractable threat to human health it represents.”
Contributors included researchers from Baylor College of Medicine; University of Texas Health Science Center at Houston; King’s College London; Hans Knoell Institute and Friedrich Schiller University Jena (Germany); and Michael E. DeBakey VA Medical Center (Houston).
Funding came from several National Institutes of Health grants as well as support from Wellcome Trust.
