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

Wolf T, Kämmer P, Brunke S, Linde J (2018) Two's company: studying interspecies relationships with dual RNA-seq. Curr Opin Microbiol 42, 7-12. (Review)
Hsieh SH, Brunke S, Brock M (2017) Encapsulation of antifungals in micelles protects Candida albicans during gall-bladder infection. Front Microbiol 8, 117.
Köhler JR, Hube B, Puccia R, Casadevall A, Perfect JR (2017) Fungi that infect humans. Microbiol Spectr 5(3), FUNK-0014-2016. (Review)
Ramírez-Zavala B, Mottola A, Haubenreißer J, Schneider S, Allert S, Brunke S, Ohlsen K, Hube B, Morschhäuser J (2017) The Snf1-activating kinase Sak1 is a key regulator of metabolic adaptation and in vivo fitness of Candida albicans. Mol Microbiol 104(6), 989-1007.
Verma AH, Richardson JP, Zhou C, Coleman BM, Moyes DL, Ho J, Huppler AR, Ramani K, McGeachy MJ, Mufazalov IA, Waisman A, Kane LP, Biswas PS, Hube B, Naglik JR, Gaffen SL (2017) Oral epithelial cells orchestrate innate type 17 responses to Candida albicans through the virulence factor candidalysin. Sci Immunol 2(17), pii: eaam8834.
Hebecker B, Vlaic S, Conrad T, Bauer M, Brunke S, Kapitan M, Linde J, Hube B, Jacobsen ID (2016) Dual-species transcriptional profiling during systemic candidiasis reveals organ-specific host-pathogen interactions. Sci Rep 6, 36055.
Jakab Á, Mogavero S, Förster TM, Pekmezovic M, Jablonowski N, Dombrádi V, Pócsi I, Hube B (2016) Effects of the glucocorticoid betamethasone on the interaction of Candida albicans with human epithelial cells. Microbiology 162(12), 2116-2125.
Pericolini E, Gabrielli E, Amacker M, Kasper L, Roselletti E, Luciano E, Sabbatini S, Kaeser M, Moser C, Hube B, Vecchiarelli A, Cassone A (2015) Secretory aspartyl proteinases cause vaginitis and can mediate vaginitis caused by Candida albicans in mice. MBio 6(3), e00724.
Gow NA, Hube B (2012) Importance of the Candida albicans cell wall during commensalism and infection. Curr Opin Microbiol 15(4), 406-412. (Review)
Wächtler B, Citiulo F, Jablonowski N, Förster S, Dalle F, Schaller M, Wilson D, Hube B (2012) Candida albicans-epithelial interactions: dissecting the roles of active penetration, induced endocytosis and host factors on the infection process. PLOS One 7(5), e36952.

Funding