Browse
Submit Data
Databases
API
Help

Dataset Information

27 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

A Comparative Transcriptome Between Anti-drug Sensitive and Resistant Candida auris in China.

ABSTRACT: Candida auris emerged as a pathogenic species of fungus that causes severe and invasive outbreaks worldwide. The fungus exhibits high intrinsic resistance rates to various first-line antifungals, and the underlying molecular mechanism responsible for its multidrug resistance is still unclear. In this study, a transcriptomic analysis was performed between two C. auris isolates that exhibited different anti-drug patterns by RNA-sequencing, namely, CX1 (anti-drug sensitive) and CX2 (resistant). Transcriptomic analysis results revealed 541 upregulated and 453 downregulated genes in the resistant C. auris strain compared with the susceptible strain. In addition, our findings highlight the presence of potential differentially expressed genes (DEGs), which may play a role in drug resistance, including genes involved in ergosterol and efflux pump biosynthesis such as SNQ2, CDR4, ARB1, MDR1, MRR1, and ERG genes. We also found that Hsp related genes were upregulated for expression in the anti-drug-resistant strain. Biofilm formation and growth conditions were also compared between the two isolates. Our study provides novel clues for future studies in terms of understanding multidrug resistance mechanisms of C. auris strains.

SUBMITTER: Zhou W

PROVIDER: S-EPMC8330549 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

The mycoparasitic yeast Saccharomycopsis schoenii predates and kills multi-drug resistant Candida auris.

Project description:Candida auris has recently emerged as a multi-drug resistant fungal pathogen that poses a serious global health threat, especially for patients in hospital intensive care units (ICUs). C. auris can colonize human skin and can spread by physical contact or contaminated surfaces and equipment. Here, we show that the mycoparasitic yeast Saccharomycopsis schoenii efficiently kills both sensitive and multi-drug resistant isolates of C. auris belonging to the same clade, as well as clinical isolates of other pathogenic species of the Candida genus suggesting novel approaches for biocontrol.

| S-EPMC6175896 | biostudies-other

Candida auris Pan-Drug-Resistant to Four Classes of Antifungal Agents.

Project description:Candida auris is an urgent antimicrobial resistance threat due to its global emergence, high mortality, and persistent transmissions. Nearly half of C. auris clinical and surveillance cases in the United States are from the New York and New Jersey Metropolitan area. We performed genome, and drug-resistance analysis of C. auris isolates from a patient who underwent multi-visceral transplantation. Whole-genome comparisons of 19 isolates, collected over 72 days, revealed closed similarity (Average Nucleotide Identity > 0.9996; Aligned Percentage > 0.9764) and a distinct subcluster of NY C. auris South Asia Clade I. All isolates had azole-linked resistance in ERG11(K143R) and CDR1(V704L). Echinocandin resistance first appeared with FKS1(S639Y) mutation and then a unique FKS1(F635C) mutation. Flucytosine-resistant isolates had mutations in FCY1, FUR1, and ADE17. Two pan-drug-resistant C. auris isolates had uracil phosphoribosyltransferase deletion (FUR1[1Δ33]) and the elimination of FUR1 expression, confirmed by a qPCR test developed in this study. Besides ERG11 mutations, four amphotericin B-resistant isolates showed no distinct nonsynonymous variants suggesting unknown genetic elements driving the resistance. Pan-drug-resistant C. auris isolates were not susceptible to two-drug antifungal combinations tested by checkerboard, Etest, and time-kill methods. The fungal population pattern, discerned from SNP phylogenetic analysis, was consistent with in-hospital or inpatient evolution of C. auris isolates circulating locally and not indicative of a recent introduction from elsewhere. The emergence of pan-drug-resistance to four major classes of antifungals in C. auris is alarming. Patients at high risk for drug-resistant C. auris might require novel therapeutic strategies and targeted pre-and/or posttransplant surveillance.

| S-EPMC9295560 | biostudies-literature

Abrogation of pathogenic attributes in drug resistant Candida auris strains by farnesol.

Project description:Candida auris, a decade old Candida species, has been identified globally as a significant nosocomial multidrug resistant (MDR) pathogen responsible for causing invasive outbreaks. Biofilms and overexpression of efflux pumps such as Major Facilitator Superfamily and ATP Binding Cassette are known to cause multidrug resistance in Candida species, including C. auris. Therefore, targeting these factors may prove an effective approach to combat MDR in C. auris. In this study, 25 clinical isolates of C. auris from different hospitals of South Africa were used. All the isolates were found capable enough to form biofilms on 96-well flat bottom microtiter plate that was further confirmed by MTT reduction assay. In addition, these strains have active drug efflux mechanism which was supported by rhodamine-6-G extracellular efflux and intracellular accumulation assays. Antifungal susceptibility profile of all the isolates against commonly used drugs was determined following CLSI recommended guidelines. We further studied the role of farnesol, an endogenous quorum sensing molecule, in modulating development of biofilms and drug efflux in C. auris. The MIC for planktonic cells ranged from 62.5-125 mM, and for sessile cells was 125 mM (4h biofilm) and 500 mM (12h and 24h biofilm). Furthermore, farnesol (125 mM) also suppresses adherence and biofilm formation by C. auris. Farnesol inhibited biofilm formation, blocked efflux pumps and downregulated biofilm- and efflux pump- associated genes. Modulation of C. auris biofilm formation and efflux pump activity by farnesol represent a promising approach for controlling life threatening infections caused by this pathogen.

| S-EPMC7213696 | biostudies-literature

Metabolic Profiling of Candida auris, a Newly-Emerging Multi-Drug Resistant Candida Species, by GC-MS.

Project description:Candidaauris, a newly-emerging Candida species, is a serious global health threat due to its multi-drug resistant pattern, difficulty to diagnose, and the high mortality associated with its invasive and bloodstream infections. Unlike C. albicans, and C.dubliniensis which can form true hyphae, C.auris grows as yeast or pseudohyphae and is capable of developing biofilms. The reasons for the inability of C.auris to form true hyphae are currently unknown. Metabolites secreted by microorganisms, including Candida, are known as important factors in controlling morphogenesis and pathogenesis. Metabolic profiling of C.auris and C. albicans cultures was performed using gas chromatography⁻mass spectrometry (GC⁻MS). Compared to C. albicans, C.auris secreted several hyphae-inhibiting metabolites, including phenylethyl, benzyl and isoamyl alcohols. Furthermore, a biofilm-forming metabolite-tyrosol-was identified. On the other hand, several other biomarkers identified from C.auris but not from C. albicans cultures may be produced by the organism to overcome the host immune system or control fungal adaptations, and hence ease its invasion and infections. The results from this study are considered as the first identification of C.auris metabolic activities as a step forward to understand its virulence mechanisms.

| S-EPMC6384714 | biostudies-literature

Sphingolipidomics of drug resistant Candida auris clinical isolates reveal distinct sphingolipid species signatures.

Project description:Independent studies from our group and others have provided evidence that sphingolipids (SLs) influence the antimycotic susceptibility of Candida species. We analyzed the molecular SL signatures of drug-resistant clinical isolates of Candida auris, which have emerged as a global threat over the last decade. This included Indian hospital isolates of C. auris, which were either resistant to fluconazole (FLCR) or amphotericin B (AmBR) or both drugs. Relative to Candida glabrata and Candida albicans strains, these C. auris isolates were susceptible to SL pathway inhibitors such as myriocin and aureobasidin A, suggesting that SL content may influence azole and AmB susceptibilities. Our analysis of SLs confirmed the presence of 140 SL species within nine major SL classes, namely the sphingoid bases, Cer, αOH-Cer, dhCer, PCer, αOH-PCer, αOH-GlcCer, GlcCer, and IPC. Other than for αOH-GlcCer, most of the SLs were found at higher concentrations in FLCR isolates as compared to the AmBR isolates. SLs were at intermediate levels in FLCR + AmBR isolates. The observed diversity of molecular species of SL classes based on fatty acyl composition was further reflected in their distinct specific imprint, suggesting their influence in drug resistance. Together, the presented data improves our understanding of the dynamics of SL structures, their synthesis, and link to the drug resistance in C. auris.

| S-EPMC7695621 | biostudies-literature

Essential Oils as a Good Weapon against Drug-Resistant <i>Candida auris</i>.

Project description:Candida auris is a recently found Candida species, mainly associated with nosocomial outbreaks in intensive care hospital settings, and unlike other Candida species, it can be transmitted through person-to-person or by contact with surfaces. C. auris is described as resistant to first-line antifungals and, consequently, associated with high mortality. Nowadays, essential oils (EOs) are known to be effective against fungal and bacterial infections. This work aimed to evaluate the effect of four EOs (tea tree, niaouli, white thyme and cajeput) against C. auris. The EO's effect on C. auris planktonic growth was evaluated by the minimum inhibitory concentration determination and by the agar disc diffusion method. Then, the same effect was evaluated on biofilm by colony-forming units' enumeration. The results showed that EOs were able to inhibit the C. auris planktonic growth, with an MIC50 between 0.78 and 1.56% and halos of 20-21 mm for white thyme and tea tree and 13-14 mm for cajeput and niaouli. In addition, the EOs were also able to completely inhibit biofilm formation. Moreover, white thyme and cajeput completely eradicate pre-formed biofilms, while tea tree and niaouli significantly reduce it. Thus, this work demonstrates that EOs are a possible therapeutic alternative and a future perspective for the hard fight against C. auris.

| S-EPMC9311903 | biostudies-literature

Mycobacterium tuberculosis clinical isolates in China: extensively drug-resistant tuberculosis vs drug sensitive one

Project description:Transcriptional profiling of mycobacterium tuberculosis clinical isolates in China comparing extensively drug-resistant tuberculosis with drug sensitive one.

2009-04-04 | GSE15540 | GEO

A biological and genomic comparison of a drug-resistant and a drug-susceptible strain of <i>Candida auris</i> isolated from Beijing, China.

Project description:The fungal pathogen Candida auris has emerged as a new threat to human health. We previously reported the first isolate of C. auris (BJCA001) in China, which belongs to the South Asian clade (I) and was susceptible to all antifungals tested. In this study, we report the isolation of a drug-resistant C. auris strain (BJCA002) from the same city (Beijing). Strain BJCA002 belongs to the South African clade (III) and is resistant to fluconazole and amphotericin B based on the tentative MIC breakpoints. Taking advantage of the two isolates with distinct antifungal susceptibility and genetic origins, we performed a biological and genomic comparative study. Besides antifungal susceptibility, strains BJCA001 and BJCA002 showed differences in multiple aspects including morphologies, expression of virulence factors, virulence, mating type, and genomic sequence and organization. Notably, strain BJCA002 was less virulent than BJCA001 in both the Galleria mellonella and mouse systemic infection models. Genomic analysis demonstrated that strain BJCA002 but not BJCA001 had multiple mutations in drug resistance-associated genes, including a hot-spot mutation of ERG11 (VF125AL, namely V125A and F126L) and some missense mutations in CDR1, MDR1, and TAC1. Notably, strain BJCA001 carried 64 copies of the Zorro3 retrotransposon, whereas BJCA002 had only 3 copies in the genome. Taken together, our findings not only reveal the genetic and phenotypic diversities of the two isolates from Beijing, China, but also shed new light on the genetic basis of the antifungal resistance and virulence of C. auris.

| S-EPMC8172162 | biostudies-literature

Mycobacterium tuberculosis clinical isolates in China: extensively drug-resistant tuberculosis vs drug sensitive one

Project description:Transcriptional profiling of mycobacterium tuberculosis clinical isolates in China comparing extensively drug-resistant tuberculosis with drug sensitive one. The same condition experiment. The samples were from the different drug-resistant strains. Only one replicate.

2009-04-04 | E-GEOD-15540 | biostudies-arrayexpress

In vitro antifungal activity of myriocin against drug-resistant Candida auris strains

Project description:Myriocin exhibited very low MIC values (0.016 to 0.4 mg/L) to all C. auris isolates including several multidrug-resistant strains. The yeast-form, filamentous, or aggregating-form cells were all susceptible to the chemical. The antifungal effect was majorly due to the fungistatic activity, although an extended treatment could lead to the fungicidal activity to C. auris cells. Transcriptomic analysis demonstrates that myriocin suppresses the cellular metabolic activity and induces the expression of stress or antifungal response genes.

2020-12-03 | GSE161599 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data