Comparative Analysis of Pathogenic Candida—Macrophage Interactions

Candida species are recognized by the World Health Organization as priority human fungal pathogens, with Candida albicans and C. auris classified in the critical priority group, while C. glabrata is included in the high priority group (Organization, 2022). These species differ in their interactions with macrophages. C. albicans interactions are characterized by a strong induction of host cell death and a pro-inflammatory response (5), whereas C. glabrata and C. auris exhibit a comparatively reduced host immune activation during infection. C. glabrata persists and grows intracellularly for several days before escaping through cell bursting (Lange et al., 2023). In contrast, based on our observations in human macrophages, C. auris is efficiently phagocytosed and escapes early with a weak inflammatory signaling and preserved host cell viability (Holt & Nett, 2024; Miramon et al., 2023). These similarities point to convergent evolution in terms of immune evasion. In addition, C. auris persists on abiotic surfaces, where it is exposed to nutrient starvation that increases its resilience and alters neutrophil responses (Allert et al., 2022). A key question is how environmental, or clinical stressors influence C. auris interactions with macrophages. We hypothesize that C. auris and C. glabrata independently evolved immune evasion strategies which are amplified by environmental pressures. By investigating how stress-priming promotes specific molecular pathways, this project aims to elucidate how these fungi evade or subvert the macrophage responses. We are currently comparing the interactions of C. auris and C. glabrata with macrophages, especially after priming with environmental and clinical stressors. This includes direct comparisons of the reaction of both fungi to immune cell-related stresses. These analyses will help us to identify stress-regulated genes and molecular pathways that sustain immune evasion in either or both species.

PhD start: 04/01/2025