Pathogenicity mechanisms at the mucosal interphase

In vitro translocation model simulates the intestinal epithelial barrier

In the healthy host, certain Candida species live as harmless commensals on mucosal surfaces like the oral, vaginal or intestinal mucosa. Under predisposing conditions, these Candida species growing on the oral or vaginal mucosa can cause tissue damage associated with induction of inflammation, immunopathology, and disease that significantly impacts quality of life.

When immune defense and microbiota are compromised in hospitalized patients or when the intestinal barrier is disturbed, fungal populations of the intestinal tract can invade the intestinal epithelial barrier and translocate into the bloodstream. From here, the fungus can infect virtually all organs and cause systemic fungal infection. Our aim is to elucidate which fungal and host factors mechanistically allow fungal adhesion to, invasion into, and damage of epithelial cells as well as translocation through intestinal barriers and invasion of host tissues.

To unravel host-pathogen interactions at the epithelial interface for C. albicans, but also C. glabrata and the newly emerged, multidrug-resistant species C. auris we are using in vitro infection models, genome-wide dual-species transcription profiling techniques, and fungal gene deletion strains.

Staff

Stefanie Allert
Lydia Kasper
Jakob Sprague

Publications

Westman J, Plumb J, Licht A, Yang M, Allert S, Naglik JR, Hube B, Grinstein S, Maxson ME (2022) Calcium-dependent ESCRT recruitment and lysosome exocytosis maintain epithelial integrity during Candida albicans invasion. Cell Rep 38(1), 110187.
Alonso-Monge R, Gresnigt MS, Román E, Hube B, Pla J (2021) Candida albicans colonization of the gastrointestinal tract: A double-edged sword. PLOS Pathog 17(7), e1009710.
Austermeier S, Pekmezović M, Porschitz P, Lee S, Kichik N, Moyes DL, Ho J, Kotowicz NK, Naglik JR, Hube B, Gresnigt MS (2021) Albumin neutralizes hydrophobic toxins and modulates Candida albicans pathogenicity. mBio 12(3), e0053121.
d'Enfert C, Kaune AK, Alaban LR, Chakraborty S, Cole N, Delavy M, Kosmala D, Marsaux B, Fróis-Martins R, Morelli M, Rosati D, Valentine M, Xie Z, Emritloll Y, Warn PA, Bequet F, Bougnoux ME, Bornes S, Gresnigt MS, Hube B, Jacobsen ID, Legrand M, Leibundgut-Landmann S, Manichanh C, Munro CA, Netea MG, Queiroz K, Roget K, Thomas V, Thoral C, Van den Abbeele P, Walker AW, Brown AJP (2021) The impact of the Fungus-Host-Microbiota interplay upon Candida albicans infections: current knowledge and new perspectives. FEMS Microbiol Rev 45(3), fuaa060. (Review)
Last A, Maurer M, Mosig AS, Gresnigt MS, Hube B (2021) In vitro infection models to study fungal-host interactions. FEMS Microbiol Rev 45(5), fuab005. (Review)
Liu J, Willems HME, Sansevere EA, Allert S, Barker KS, Lowes DJ, Dixson AC, Xu Z, Miao J, DeJarnette C, Tournu H, Palmer GE, Richardson JP, Barrera FN, Hube B, Naglik JR, Peters BM (2021) A variant ECE1 allele contributes to reduced pathogenicity of Candida albicans during vulvovaginal candidiasis. PLoS Pathog 17(9), e1009884.
Pekmezovic M, Hovhannisyan H, Gresnigt MS, Iracane E, Oliveira-Pacheco J, Siscar-Lewin S, Seemann E, Qualmann B, Kalkreuter T, Müller S, Kamradt T, Mogavero S, Brunke S, Butler G, Gabaldón T, Hube B (2021) Candida pathogens induce protective mitochondria-associated type I interferon signalling and a damage-driven response in vaginal epithelial cells. Nat Microbiol 6(5), 643-657.
Pekmezovic M, Kalagasidis Krusic M, Malagurski I, Milovanovic J, Stępień K, Guzik M, Charifou R, Babu R, O'Connor K, Nikodinovic-Runic J (2021) Polyhydroxyalkanoate/Antifungal polyene formulations with monomeric hydroxyalkanoic acids for improved antifungal efficiency. Antibiotics (Basel) 10(6), 737.
Pekmezovic M, Kaune AK, Austermeier S, Hitzler SUJ, Mogavero S, Hovhannisyan H, Gabaldón T, Gresnigt MS, Hube B (2021) Human albumin enhances the pathogenic potential of Candida glabrata on vaginal epithelial cells. PLoS Pathog 17(10), e1010037.
Ho J, Wickramasinghe DN, Nikou SA, Hube B, Richardson JP, Naglik JR (2020) Candidalysin is a potent trigger of alarmin and antimicrobial peptide release in epithelial cells. Cells 9(3), 699.

Funding