In FunHoMic, 13 ESRs have been hired and have undertaken their respective research programs at the Partner institutions. Despite the major impact of the COVID-19 pandemics on the functioning of the laboratories, all ESRs have made significant progress in their research projects and the following achievements are to be pinpointed:
• A bioinformatics pipeline and fungal gene catalog, called FunOMIC, has been developed enabling both taxonomic and functional profiling of fungal genes. A corresponding user-friendly web server, Mycodm, has been developed.
• A fungal enrichment protocol has been developed.
• A cell line-derived gut-on-chip model has been optimized for studying fungal pathogenesis and applied to the study of a fungal peptide toxin, candidalysin, and the effect of short chain fatty acids.
• A patient-derived colon organoid gut-on-chip model has been developed and attempts to develop an oral mucosa-on-chip model were made.
• The Simulator of Human Intestinal Microbial Ecosystem (SHIME) system was shown to represent a valuable model to investigate fungal colonization in different gut compartments.
• Understanding of the genotypic and phenotypic specificities of the Candida africana cluster within the Candida albicans species was obtained.
• Exometabolome studies revealed extensive isolate-specific utilization of metabolites as well as cluster-specific differences, most notably the delineation of the C. africana cluster (impaired trehalose and choline utilization).
• Mutation pressure in cell wall-related genes was analysed, revealing genetic cluster-specific patterns. Genes harbouring potential cluster-specific gain-of-function mutations relevant to adhesion and biofilm formation have been pinpointed. Sensitivity to cell wall-perturbating agents also showed cluster-specificity.
• Antibiotic-induced alterations in the microbiota composition was shown to significantly aggravate systemic candidiasis progression.
• Gut colonization by C. albicans itself was shown to protect from systemic infection, with variation of this effect according to the colonizing C. albicans strain.
• A role of lactic acid, as well as acetic acid, in the outcome of the interaction of C. albicans with the host in the vaginal niche was observed.
• IL-17-dependent antimicrobial peptides have been identified at the origin for the IL-17-mediated restriction of C. albicans virulence in the oral niche.
• Two candidate host proteins, which may serve prognostic marker in RVVC have been identified.
• Analysis of C. albicans gastro-intestinal carriage in healthy individuals revealed factors that influence the level of carriage: diet-associated factors, host genetics.
• A culturomics approach performed using fecal sample from a healthy donor identified 11 bacterial strains with potential anti-Candida activities.
• Safety assessment of some candidate LBPs has been performed.
• The potentiation of the already commercialized LBP Lactobacillus rhamnosus Lcr35 by sodium thiosulfate was ascribed to the conversion of STS into sulfur.
• Elevated levels of short chain fatty acids (SCFAs) could explain the activity of LBPs towards C. albicans.
Importantly, work by the FunHoMic ESRs has led to 13 publications.
