Virulence not required? Albumin promotes pathogenicity of (non)-damaging Candida strains

Abstract Poster session 3, September 23, 2022, 12:30 PM - 1:30 PM The pathogenicity of the dimorphic yeast Candida albicans is associated with filamentation, adhesion, invasion, and production of the toxin Candidalysin. However, there are certain clinical isolates and other Candida spp., that cause infection independent of filamentation or the production of Candidalysin. Consequently, these strains and species are often non-damaging in vitro, this does not correlate with their potential to cause infection in patients. We hypothesize that specific host factors, which trigger pathogenicity, are absent in in vitro models, and thereby not reflecting the situation in the host. To determine the impact of albumin, the most abundant protein in the human body, vaginal epithelial cells were infected with different C. albicans strains and Candida species. Interestingly, after prolonged infection (45 h) albumin increased the damage potential, even in otherwise non-damaging and non-filamentous strains. This included deletion mutants deficient in filamentation, als3 adhesin/invasin, thigmotropism, or Candidalysin production. Yet, the increased damage was likely not solely an effect of increased growth and nutrient competition between the fungus and epithelial cells. Reduced damage in presence of protease inhibitors and albumin hint toward the role of proteases in the utilization of albumin. Albumin enhanced C. albicans metabolism, by stimulating the utilization of various nitrogen sources. This metabolic adaption could explain the advantage and enhanced growth as a strain and species-independent feature. Our data suggest that common host factors can impact C. albicans to cause damage independent of adhesion, invasion, filamentation, and toxin production. Possibly, also other host-derived factors can drive the pathogenic potential of fungi through unresolved mechanisms.