RNA sequencing of C. auris and C. albicans under different conditions
Ontology highlight
ABSTRACT:
ORGANISM(S): Candida albicans Candidozyma auris
PROVIDER: GSE255158 | GEO | 2026/01/12
REPOSITORIES: GEO
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Project description:The rise of drug-resistant fungal species, such as Candida auris, poses a serious threat to global health, with mortality rates exceeding 40% and resistance rates surpassing 90%. The limited arsenal of effective antifungal agents underscores the urgent need for novel strategies. Here, we systematically evaluate the role of histone H3 post-translational modifications in C. auris drug resistance, focusing on acetylation mediated by Gcn5 and Rtt109, and methylation mediated by Set1, Set2, and Dot1. Mutants deficient in these enzymes exhibit varying degrees of antifungal drug sensitivity. Notably, we discover that GCN5 depletion and the subsequent loss of histone H3 acetylation downregulates key genes involved in ergosterol biosynthesis and drug efflux, resulting in increased susceptibility to azoles and polyenes. Additionally, Gcn5 regulates cell wall integrity and echinocandin resistance through the calcineurin signaling pathway and transcription factor Cas5. In infection models using Galleria mellonella and immunocompromised mice, GCN5 deletion significantly reduces the virulence of C. auris. Furthermore, the Gcn5 inhibitor CPTH2synergizes with caspofungin in vitro and in vivo without notable toxicity. These findings highlight the critical role of Gcn5 in the resistance and pathogenicity of C. auris, positioning it as a promising therapeutic target for combating invasive fungal infections.
2025-04-05 | GSE293594 | GEO
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:The ‘superbug’ Candida auris has been ranked as a priority fungal pathogen and is becoming a serious threat to public health. However, the underlying mechanisms of real-world pathogen-host interactions remain elusive, in part due to the lack of powerful immunocompetent animal models. In this study, we report that selected wild-type strains of Drosophila melanogaster can be developed as a promising infection model to recapitulate C. auris bloodstream infection. The systemic and organ-specific responses to C. auris infection in vivo were evaluated, as well as the corresponding transcriptional profiling. Our findings confirm that Toll and JAK-STAT signaling pathways mediate antifungal responses in the Drosophila model following C. auris infection. Moreover, we identified certain conserved novel factors required for host-C. auris interactions, highlighting the fly model's potential to reveal subtle immune mechanisms not readily observed in mammalian systems. Taken together, our work demonstrates that wild-type Drosophila offers a robust immunocompetent animal model for the further in-depth investigation of dynamic C. auris-host interactions in vivo.
2025-10-12 | GSE279369 | GEO
Project description:Candida auris is an emerging infectious agent and WHO critical priority fungal pathogen. Rising pan-resistance, massive nosocomial outbreaks and diagnostic challenges complicate clinical treatment, with an associated human mortality rate of 45%. Importantly, in vivo gene expression of C. auris during infection has not been described to date. We developed the novel thermotolerant teleost fish embryo yolk-sac microinjection model of Aphanius dispar (Arabian Killifish, AK) for infection by each of the five major C. auris clades. This model enabled dual host-pathogen RNA-seq at 24 and 48 hours post injection (HPI) at mammalian temperature (37 °C), which has not been reported in other teleost fish models. Host gene expression indicated features of nutritional and innate immune responses, including haem-oxygenase and C-type lectin receptor expression. We identified an in vivo transcriptome signature common to all five clades of C. auris compared to in vitro expression that was highly enriched for putative xenosiderophore transmembrane transporters. We describe the seventeen-member xenosiderophore transport candidate family in terms of diverse in-host patterns of expression and cross-kingdom functional prediction. We discovered that only the basal clade V isolate formed filaments in vivo, corresponding with Candida-typical and atypical hypha-formation genetic signals, such as the novel adhesin SCF1. Furthermore, clades that were more virulent (I or IV vs II or III) were strongly characterised by upregulation of the majority of genes at the mating-type locus (MTL), including non-mating genes, consistent with a role for the MTL in C. auris pathogenicity. We hypothesise that both xenosiderophore transport genes and the MTL may play critical roles in C. auris virulence, and are urgent targets for potential therapy.
2025-11-13 | GSE277854 | GEO
Project description:Candida auris (Candidozyma auris) is a yeast pathogen that poses a public health threat because of its ability to develop antifungal resistance. Notably, most C. auris isolates are resistant to fluconazole. The efflux pump Cdr1 is a key contributor of azole resistance in C. auris. In C. albicans, Cdr1 is regulated by the transcription factor Tac1, which has two orthologs in C. auris (Tac1a and Tac1b). While the role of Tac1b has been described, little is known about Tac1a. In this study, we characterized the respective roles of Tac1a and Tac1b in azole resistance. To investigate their transcriptional regulation and binding targets, we performed RNA sequencing and ChEC-seq (Chromatin endogenous cleavage sequencing) for both transcription factors. RNA sequencing was carried out by comparing hyperactivated mutants (TAC1a-HA or TAC1b-HA) with the wild-type strain IV.1. ChEC-seq was performed in strains carrying endogenous C-terminal MNase fusions (TAC1a-MNase and TAC1b-MNase) and in a control strain expressing ectopically MNase (Free MNase). Both Tac1a and Tac1b mediate azole resistance in C. auris via regulation of Cdr1, with overlapping downstream targets and evidence of autoregulation.
2025-09-13 | GSE307436 | 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:CDC Mycotic Diseases Branch Candida auris pathogen surveillance
| PRJNA1167312 | ENA
Project description:Candida auris is an emerging multidrug-resistant human fungal pathogen often refractory to treatment by all classes of antifungal drugs. Amphotericin B (AmB) is a fungicidal drug that, despite its toxic side effects, remains a drug of choice for the treatment of drug-resistant fungal infections, including those caused by C. auris. However, the molecular mechanisms underlying AmB resistance are poorly understood. In this study, we present data that suggests membrane lipid alterations and chromatin modifications are critical processes that contribute to or cause adaptive AmB resistance in clinical C. auris isolates. To determine the plausible cause of increased AmB resistance, we performed RNA-seq of AmB-resistant and sensitive C. auris isolates. Remarkably, AmB-resistant strains show a pronounced enrichment of genes involved in lipid and ergosterol biosynthesis, adhesion, drug transport as well as chromatin remodeling. The transcriptomics data confirm increased adhesion and reduced lipid membrane permeability of AmB-resistant strains compared to the sensitive isolates. The AmB-resistant strains also display hyper-resistance to cell wall perturbing agents, including congo red, calcofluor white and caffeine. Additionally, we noticed an increased phosphorylation of Mkc1 cell integrity MAP kinase upon AmB treatment. Collectively, these data identify differences in the transcriptional landscapes of AmB-resistant vs AmB-senstive isolates, and provide a framework for the mechanistic understanding of AmB resistance in C. auris.
2022-05-02 | GSE190920 | GEO
Project description:Candida auris is an emerging fungal pathogen known for its high resistance to fluconazole, the most commonly prescribed antifungal. However, the genetic regulators of fluconazole susceptibility remain insufficiently understood in C. auris. Using a pooled screen of piggyBac (PB) transposition mutants, we identify significant enrichment of mitochondrial genes whose inactivation causes reduced fluconazole susceptibility. Genome-wide genetic interaction analysis of a representative mitochondrial gene-deleted mutant, pet309Δ, implicates that mitochondrial dysfunction reduces fluconazole susceptibility by enhancing Cdr1 efflux activity post-transcriptionally and through the vacuolar calcium pump homolog Cdt1. We further demonstrate that Cdt1, beyond its canonical calcium-pumping function, mediates fluconazole efflux, evidenced by its fluconazole-induced, calcineurin-dependent plasma membrane localization and dependence on ATP hydrolysis. Additionally, Cdt1 accelerates the evolution of fluconazole resistance, and its transcript levels correlate with susceptibility across clinical isolates. Our findings define a novel role for Cdt1 in fluconazole efflux in C. auris.
2026-01-06 | GSE300783 | GEO
Project description:Candida auris has emerged as a problematic fungal pathogen associated with high morbidity and mortality. Amphotericin B (AmB) is the most effective antifungal used to treat invasive fungal candidiasis, with resistance rarely observed among clinical isolates. However, C. auris possesses extraordinary resistant profiles against all available antifungal drugs, including AmB. In our pursuit of potential solutions, we conducted a screening of a panel of 727 FDA-approved drugs and identified the proton pump inhibitor lansoprazole (LNP) as a potent enhancer of AmB’s activity against C. auris. LNP also potentiates the antifungal activity of AmB against other medically important species of Candida and Cryptococcus. Our investigations into the mechanism of action unveiled that LNP metabolite(s) interact with a crucial target in the mitochondrial respiratory chain (complex III, known as cytochrome bc1). This interaction increases oxidative stress within fungal cells. Our results demonstrated the critical role of an active respiratory function in the antifungal activity of LNP. Most importantly, LNP restored the efficacy of AmB in an immunocompromised mouse model, resulting in a 1.7-log (~98%) CFU reduction in the burden of C. auris in the kidneys. Our findings strongly advocate for a thorough and comprehensive evaluation of LNP as a cytochrome bc1 inhibitor for combating drug-resistant C. auris infections.
2024-03-13 | GSE244094 | GEO