Year: 2026
Type: article
Abstract: ABSTRACT Strains of food-derived microbes can become facultative pathogens in susceptible human hosts. Surprisingly, we previously isolated Debaryomyces hansenii , a yeast common in fermented foods, from Crohn disease (CD) ulcers, raising questions about its strain-specific traits that influence host interactions. Here, we further developed the genetic tractability of D. hansenii and identified a single adhesin, Hil1, as a major determinant of colony morphology, biofilm formation, and immune targeting in CD patients. We used Agrobacterium tumefaciens -mediated transformation to perform a forward genetic screen in a food-derived reference strain. We isolated mutants that converted from a wrinkled, biofilm-forming phenotype to a smooth, non-adherent phenotype characteristic of CD patient isolates. Mapping of multiple insertion sites showed a disrupted subtelomeric Hyr/Iff-like adhesin gene, herein referred to as HIL1 . CRISPR-Cas9-mediated deletion of HIL1 recapitulated the mutant phenotype, demonstrating that HIL1 was necessary for biofilm formation and high cell-surface hydrophobicity phenotypes. To contextualize these findings, we performed comparative genomics on a D. hansenii strain collection to assess allelic variation in the number of HIL1 tandem repeats. Longer alleles in food strains correlated with increased biofilm formation, while CD-isolated strains contained shorter HIL1 alleles and reduced binding to surfaces. Serology profiling showed that HIL1 was a direct antigenic target of circulating immunoglobulin G (IgG) in CD patients. Together, these results suggest Hil1 is a key, strain-variable adhesin shaping fungal surface properties and host immune recognition. This work establishes D. hansenii as a genetically tractable system and shows how adhesin polymorphisms may influence fungal behavior in food and disease contexts. IMPORTANCE Debaryomyces hansenii is a yeast that is common in food and is generally recognized as safe for human consumption, though recently it has been identified within diseased regions of the intestine in Crohn disease patients. A current need is to determine the genetic and phenotypic differences between safe food isolates and isolates from human Crohn disease patient ulcers. Here, we used a loss-of-function genetic screen and identified HIL1 , an adhesin that we found mediates cellular adhesion in many food strains but not in patient strains. We identified circulating HIL1 -reactive antibodies in patients with Crohn disease, indicating that food strains can be a target of host immune responses through Hil1.
Source: mBio
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,900
Funders: U.S. Department of Energy, Cleveland Clinic, University of Texas Southwestern Medical Center, Dartmouth College, Universite Angers, National Institutes of Health, Office of Science, National Cancer Institute, National Institute of General Medical Sciences, National Institute of Allergy and Infectious Diseases, National Institute of Diabetes and Digestive and Kidney Diseases, Basic Energy Sciences, Chemical Sciences, Geosciences, and Biosciences Division
Awards: Acquisition of the NextSeq2000 Sequencing platform to Increase Next Generation Sequencing Throughput While Reducing Costs at Dartmouth, G1127861144, G14835683, G1497563064, G1556230741, G1830523874, G209265959, G283689134, G3196151346, G3700436328, G3943430667, G4060338706, G4864440416, G540597685, G5593201721, G6245215520, G7044953335, G7321402606, G776528767, G834722375, G8400948363, G9000004006, G9000021360, G9000027953, G9000084893, G9000146921, G9000151325, G9000300661, G9000325178, The Institute for Biomolecular Targeting, THE CENTER FOR PLANT AND MICROBIAL COMPLEX CARBOHYDRATES AT THE UNIVERSITY OF GEORGIA COMPLEX CARBOHYDRATE RESEARCH CENTER
OpenAlex ID: W7171812447