Project description:PAT-seq approach was utilised to determine the gene expression in the the transcriptome of C. auris treated with the vehicle DMSO or drug pyrvvinium pamoate (PP). Biological triplicates of C. auris cultures grown in RPMI medium with either DMSO or 1uM PP for 30 minutes at 37 Celsius were havested and total RNA was isolated using standard procedures (hot phenol method).
Project description:Interventions: Group 1: Quantitative Expression Analysis of the proteom and gene Expression of Primary Tumor, normal tissue, and metastases
Primary outcome(s): Disease associated Proteins and Genes
Study Design: Allocation: ; Masking: ; Control: ; Assignment: ; Study design purpose: basic science
Project description:Candida auris is amongst the most important emerging fungal pathogens, yet mechanistic insights in its immune recognition and control are lacking. Here, we integrate transcriptional and functional immune cell profiling to uncover innate anti-C. auris defense mechanisms. C. auris induces a specific transcriptome in human mononuclear cells, a stronger cytokine response compared to C. albicans, but a lower macrophage lysis capacity. C. auris-induced innate immune activation is mediated through recognition of C-type lectin receptors, mainly elicited by structurally unique C. auris mannoproteins. In in-vivo experimental models of disseminated candidiasis, C. auris was less virulent than C. albicans. Collectively, these results demonstrate that C. auris is a strong inducer of innate host defense and identify possible targets for adjuvant immunotherapy.
Project description:In this study, we designed a novel antifungal agent, PQA-Az-13 that demonstrated antifungal activity against C. auris biofilms. Cellular proteomics indicated that PQA-Az-13 partially or completely inhibited numerous enzymatic proteins in C. auris biofilms, particularly those involved in both amino acid biosynthesis and metabolism processes, as well as in general energy-producing processes. Due to its hydrophobic nature and limited aqueous solubility, PQA-Az-13 was encapsulated in cationic liposomes and characterized by biophysical and spectral techniques. PQA-Az-13 liposomes demonstrated enhanced antifungal activity levels against both C. auris in in vitro biofilms and ex vivo skin colonization models.
Project description:Candida auris has been globally recognized as a multidrug-resistant human fungal pathogen that contributes for the worldwide occurrence of nosocomial outbreaks. It has been reported that C. auris was able to avoid neutrophil attack, suggestive of an impaired innate immune response. Whether C. auris evades the innate immune recognition of BMDM (bone marrow derived macrophage) remains poorly understood, and as for well-known Candida species -C. albicans, it can trigger immune response. To determine whether occurs difference between immune response stimulated by C. auris or C. albicans, we performed mRNA-seq of BMDM stimulated by C. auris or C. albicans.