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Candida non-albicans biofilm-derived vesicles

ABSTRACT: Currently, non-albicans Candida species, including C. tropicalis, C. glabrata and C. parapsilosis, are becoming an increasing epidemiological threat, predominantly due to the distinct collection of virulence mechanisms, as well as emerging resistance to the antifungal drugs typically used in the treatment of candidiasis. They can produce biofilms that release extracellular vesicles (EVs) ‒ nanometric spherical structures surrounded by a lipid bilayer, transporting diversified biologically active cargo, that may be involved in intercellular communication, biofilm matrix production, and interaction with host.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Candida Tropicalis Mya-3404

TISSUE(S): Fungal Cell

SUBMITTER: Justyna Karkowska-Kuleta

LAB HEAD: Maria Rapala-Kozik

PROVIDER: PXD033300 | Pride | 2022-06-23

REPOSITORIES: Pride

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Candida non-albicans biofilm-derived extracellular vesicles

Project description:Currently, non-albicans Candida species, including C. tropicalis, C. glabrata and C. parapsilosis, are becoming an increasing epidemiological threat, predominantly due to the distinct collection of virulence mechanisms, as well as emerging resistance to the antifungal drugs typically used in the treatment of candidiasis. They can produce biofilms that release extracellular vesicles (EVs) ‒ nanometric spherical structures surrounded by a lipid bilayer, transporting diversified biologically active cargo, that may be involved in intercellular communication, biofilm matrix production, and interaction with host.

2022-06-23 | PXD033327 | Pride

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Transcriptional responses of primary murine macrophages to four Candida species

Project description:Candidiasis is an infection caused by yeasts of the genus Candida that ranges in severity from debilitating mucosal infections to disseminated disease with high mortality rates. C. albicans is the most common cause of infection, but non-albicans species collectively represent a significant disease burden. Disseminated disease rarely affects immunocompetent individuals, largely due to the action of innate immune cells, including macrophages, in controlling infection. The interaction of C. albicans with macrophages has been subject to extensive study, but there has been little investigation of the macrophage response to non-albicans Candida species. Here, we used RNA-seq to investigate global transcriptional changes within primary murine macrophages after one hour in response to four species: C. albicans, C. parapsilosis, C. tropicalis and Clavispora lusitaniae. We identified a strong pro-inflammatory response to C. albicans that was largely independent of fungal variability and found that this was highly correlated with the response to C. parapsilosis and C. tropicalis. In contrast, C. lusitaniae elicited a broadly weaker response, including reduced induction of cytokine genes. Several chemokine genes also showed weaker induction in response to both C. lusitaniae and C. parapsilosis than to C. albicans, although significantly reduced secretion of CCL3 protein was only evident in response to C. lusitaniae. These data indicate a high degree of similarity in early macrophage recognition of multiple important Candida pathogens, but also suggest that weaker recognition of C. lusitaniae by immune cells may aid immune evasion by this species.

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Filamentation is Associated with Reduced Pathogenicity of Multiple Non-albicans Candida Species

Project description:Candidiasis affects a wide variety of immunocompromised individuals, including HIV/AIDS patients and cancer patients on chemotherapy. Candida albicans, a major human fungal pathogen, accounts for about 50% of all cases, while the remainder are caused by the less pathogenic non-albicans Candida species (NACS). These species are believed to be less pathogenic, in part, because they do not filament as readily or robustly as C. albicans, although definitive evidence is lacking. To address this question, we used strains for two NACS, Candida tropicalis and Candida parapsilosis, that are genetically engineered to constitutively express the key transcriptional regulator UME6 and drive strong filamentation both in vitro and during infection in vivo. Unexpectedly, both strains showed a dramatic reduction in organ fungal burden and clearance of infection in response to UME6 expression. Consistent with these findings, we observed that a C. tropicalis hyperfilamentous mutant was significantly reduced and a filamentation-defective mutant was slightly increased for organ fungal burden. Comprehensive immune profiling did not reveal any significant changes in the host immune response to UME6 expression in the NACS. Interestingly, however, whole-genome transcriptional profiling indicated that while genes important for filamentation were induced by UME6 expression in C. tropicalis and C. parapsilosis, other genes involved in a variety of processes important for pathogenesis were strongly down-regulated. Our findings are significant because they suggest fundamental evolutionary differences in the relationship between morphology and pathogenicity among Candida species and that NACS do not necessarily possess the same virulence properties as C. albicans.

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