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�������� 80% of people have the fungus Candida albicans in their gut. Although most of the time it persists unnoticed for years causing no health problems, C. albicans can turn into a dangerous microbe that causes serious diseases in many organs, including the urinary tract, lungs and brain. Understanding how this fungus colonizes the gut is key to preventing it from becoming harmful.

Working with a mouse model, researchers at �������� and international collaborators have discovered unexpected factors that help C. albicans settle and persist in the gut. The findings expand our knowledge of the fungus-gut interactions and offer potential solutions to reduce colonization. The study appeared in Microbiology Spectrum.

“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, Corry and their colleagues explored how C. albicans colonizes the gut under healthy, unmodified conditions, which reflect real-life scenarios. They were expecting that C. albicans would not be able to colonize the animal’s gut. To their surprise, they found that a clinical strain, called CLCA10, could persist in the mouse gut for at least 58 days without causing weight loss, inflammation or disrupting the gut’s bacterial balance. Furthermore, treatment with anti-fungal medication reduced, but did not eliminate the fungus.

The fungus remained mostly associated with the gut’s contents and the mucus layer. In healthy mice, other human-associated fungal species did not colonize the gut, suggesting that something different about C. albicans affected its ability to establish itself in the gut.

The researchers were expecting to identify factors in the mouse, such as sex, diet or commercial source, that would influence the ability of C. albicans to colonize. “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.”

The team also expected that factors linked to C. albicans, such as the production of a short protein or peptide toxin called candidalysin, would not favor colonization. Candidalysin is a major contributor to C. albicans virulence. This toxin is secreted by C. albicans hyphae, a thread-like form of the fungus; it damages host cells and triggers inflammatory immune responses.

“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.”

Other contributors to this work include Pedro Miramón, Michael C. Lorenz, Léa Lortal, Julian R. Naglik, Bernhard Hube, Lynn Bimler and Farrah Kheradmand. The authors are affiliated with one or more of the following institutions: ��������, the University of Texas Health Science Center at Houston, King’s College London, Hans Knoell Institute in Germany,

Friedrich Schiller University Jena in Germany and Michael E. DeBakey VA Medical Center in Houston.

This research is supported by the National Institutes of Health grants (NIH) HL140398, R01AI135803, 1K01AG083119, 1T32HL139425, DE022550 and 5T32HL007747 and the National Institute of General Medical Sciences of the NIH under Award Number T32GM136554. Further support was provided by the Wellcome Trust (grant 214229_Z_18_Z).