Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1073457 | ENA |
REPOSITORIES: ENA
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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.
2022-05-21 | GSE203508 | GEO
Project description:Candida auris occupies similar niches in various infections as Pseudomonas aeruginosa; however, the details of their interspecies communication remain largely unknown. To gain deeper insights into this bacterial–fungal relationship, phenotypic and transcriptomic analyses were conducted in the presence of the primary P. aeruginosa quorum-sensing molecule, 3-oxo-C12-homoserine lactone (HSL), against C. auris, with the results compared to those of C. albicans. We demonstrated a significant HSL-induced reduction in adhesion of C. auris cells at 100- and 200-μM concentrations. Furthermore, HSL exposure reduced intracellular iron and zinc levels and modulated C. auris metabolism toward beta-oxidation, which may be associated with the observed reduction in in vivo virulence at lower HSL concentrations compared with C. albicans. RNA-sequencing transcriptome analysis revealed 67 and 306 upregulated genes, as well as 111 and 168 downregulated genes, in response to 100 and 200 μM HSL, respectively. We identified 45 overlapping upregulated and 25 overlapping downregulated genes between the two HSL concentrations. Our findings indicate that HSL-induced effects are not specific to C. albicans; additionally, several characteristics are present in C. auris but not in C. albicans following HSL exposure. Similar to other Candida-derived C12 compounds (e.g., farnesol), HSL reduces several C. auris survival strategies, which may significantly influence the nature of P. aeruginosa–C. auris co-habitation.
2024-07-10 | GSE271513 | GEO
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.
2020-07-23 | GSE154911 | GEO
Project description:Candida auris is a recently found pathogenic yeast that causes systemic infections, showing a high mortality rate. The delay on making a correct diagnosis of C. auris is a current problem in the healthcare system setting. As immunoproteomics studies are important to identify immunoreactive proteins for new diagnostic strategies, in this study immunocompetent murine systemic infections caused by non-aggregative and aggregative phenotypes of C. auris, and by Candida albicans and Candida haemulonii were carried out, and the obtained sera were used to study their immunoreactivity against C. auris proteins. The aim was to identify the most immunoreactive antigens of this yeast. Thirteen spots were recognized by sera from mice infected with both C. auris phenotypes and analyzed by mass spectrometry. They corresponded to enolase, phosphoglycerate kinase, glyceraldehyde 3-phosphate dehydrogenase and phosphoglycerate mutase. These four proteins seem to be also recognized by sera obtained from human patients with disseminated C. auris infection, but not by sera obtained from mice infected with other fungi such as C. albicans or Aspergillus fumigatus. In conclusion, this study showed that the identified proteins could be potential candidates to be studied as new diagnostic or even therapeutic targets for C. auris.
2024-06-23 | PXD049077 | Pride
Project description:we performed mitochondrial proteomic analysis on multiple Candida species (C. albicans, C. glabrata, C. krusei and Candida auris) and analyzed the differentially expressed mitochondrial proteins (DEMPs) between azole-sensitive and azole-resistant Candida species.
2023-09-05 | PXD045101 |
Project description:The limited number of antifungals and the emergence of multidrug-resistant Candida auris pose a significant challenge to human medicine. Here, we utilized combinatorial drug therapy as an approach to augment the activity of current azole antifungals against C. auris. We evaluated the fluconazole chemosensitization activity of 1547 FDA-approved drugs and clinical molecules against an azole-resistant strain of C. auris. This led to the discovery that lopinavir, an antiviral drug, is a potent agent capable of sensitizing C. auris to the effect of azole antifungals. At a therapeutically achievable concentration (4-8 µg/ml), lopinavir exhibited potent synergistic interactions with azole drugs, particularly with itraconazole, against C. auris (ΣFICI ranged from 0.05-0.50). The lopinavir/itraconazole combination enhanced the survival rate of C. auris-infected Caenorhabditis elegans by 90% and reduced the fungal burden in infected nematodes by 88.5% (p < 0.05). Moreover, lopinavir enhanced the antifungal activity of itraconazole against other medically important Candida species including C. albicans, C. tropicalis, C. glabrata, C. tropicalis, and C. parapsilosis. Comparative transcriptomic profiling revealed that lopinavir interferes with glucose permeation and ATP synthesis. This compromises the function of the efflux pumps presents in C. auris enhancing sensitivity to azole antifungals, as demonstrated by Nile red efflux assays. This study presents lopinavir as a novel, potent and broad-spectrum azole chemosensitizing agent that warrants further investigation against recalcitrant Candida infections.
2020-10-06 | GSE148341 | GEO
Project description:Combination therapies can be a promising tool to augment the antifungal activity of azole drugs against resistant Candida species. Here, we report the interaction between aprepitant, an antiemetic agent, and azole drugs against different Candida species including the emerging multidrug-resistant C. auris. Particularly, aprepitant enhanced the antifungal activity of itraconazole against C. auris by reducing its minimum inhibitory concentration (MIC) by 2-8 folds. Using Caenorhabditis elegans as an in vivo infection model, the aprepitant/itraconazole combination significantly prolonged the survival of the infected nematodes by ~90% and reduced the fungal burden by ~92% relative to the untreated control. Interestingly, the aprepitant/itraconazole combination exerted a potent fungicidal activity against both planktonic and adherent C. auris biofilms. Further, aprepitant/itraconazole displayed broad-spectrum synergistic interactions against other medically important Candida species including C. albicans, C. krusie, C. tropicalis, and C. parapsilosis (ƩFICI ranged from 0.08 to 031). Comparative transcriptomic profiling indicated aprepitant/itraconazole interferes significantly with metal ions homeostasis and compromises the ROS (reactive oxygen species) detoxification ability of C. auris. This study presents aprepitant as a novel, potent and broad-spectrum azole chemosensitizing agent that warrants further investigation.
2020-10-19 | GSE148749 | GEO
Project description:Candida auris has emerged as a significant healthcare-associated pathogen, posing a serious challenge due to its multidrug-resistant nature. Given the pre-existing constraints in the discovery and provision of new antifungals, there is thus an urgent imperative to design effective strategies to tackle this pressing global concern. Here, we screened a chemical library and identified phenyl-carbohydrazide derivatives with potent activity against both C. auris and the most prevalent human fungal pathogen, C. albicans. SPB00525 (N'-(2,6-Dichlorophenyl)-5-nitro-2-furohydrazide) exhibited potent activity against different strains that were resistant to standard antifungals. Using drug-induced haploinsufficient profiling, transcriptomics and metabolomic analysis, we uncovered that Ole1, a ∆(9) fatty acid desaturase, is most likely the target of SPB00525. We also found that another SPB00525 analog, HTS06170 (N'-(2,6-Dichlorophenyl)-4-methyl-1,2,3-thiadiazole-5-carbohydrazide) had a superior antifungal activity against both C. auris and C. albicans. Both SPB00525 and HTS06170 act as antivirulence agents and inhibited the invasive hyphal growth and biofilm formation of C. albicans. SPB00525 and HTS06170 attenuated fungal damage to human enterocytes and ameliorate survival of Galleria mellonella larvae used as a model of systemic candidiasis. These data, suggest that inhibiting ∆(9) fatty acid desaturase activity represents a potential therapeutic approach for treating fungal infection caused by the superbug C. auris and the most prevalent human fungal pathogen, C. albicans.
2024-05-13 | GSE267057 | GEO
Project description:Candida auris clade III isolate B12039 was spread on YPD plate supplemented with 128 µg/ml fluconazole. Randomly 39 adaptors were chosen for further analysis. We did sequencing of them as as well as the parent.
2021-06-21 | E-MTAB-10560 | biostudies-arrayexpress
Project description:Candida auris clade III isolate B11221 was spread on YPD plate supplemented with 8 µg/ml tunicamycin. Randomly 18 adaptors were chosen for further analysis. We did sequencing of these 18 adaptors as well as the parent.
2021-06-17 | E-MTAB-10536 | biostudies-arrayexpress