Antifungal susceptibility profiles and drug resistant mechanisms of clinical Candida catenulata isolates
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PROVIDER: PRJNA757701 | ENA |
REPOSITORIES: ENA
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Project description:Antifungal susceptibility profiles and drug resistant mechanisms of clinical Candida catenulata isolates
| PRJNA757603 | ENA
Project description:Antifungal susceptibility profiles and drug resistant mechanisms of clinical Candida catenulata isolates
| PRJNA757630 | ENA
Project description:Diutina catenulata (Candida catenulata) is an ascomycete yeast species widely used in environmental and industrial research and capable of causing infections in humans and animals. At present, there are only a few studies on D. catenulata, and further research is required for its more in-depth characterization and analysis. Eleven strains of D. catenulata collected from China Hospital Invasive Fungal Surveillance Net (CHIF-NET) and the CHIF-NET North China Program were identified using matrix-assisted laser desorption ionization-time of flight mass spectrometry and internal transcribed spacer sequencing. The antifungal susceptibility of the Diutina catenulata strains was tested using the Clinical and Laboratory Standards Institute broth microdilution method and Sensititre YeastOne™. Furthermore, ERG11 and FKS1 were sequenced to determine any mutations related to azole and echinocandin resistance in D. catenulata. All isolates exhibited low minimum inhibitory concentration (MIC) values for itraconazole (0.06-0.12 μg/ml), posaconazole (0.06-0.12 μg/ml), amphotericin B (0.25-1 μg/ml), and 5-flucytosine (range, <0.06-0.12 μg/ml), whereas four isolates showed high MICs (≥4 μg/ml) for echinocandins. Strains with high MIC values for azoles showed common ERG11 mutations, namely, F126L/K143R. In addition, L139R mutations may be linked to high MICs of fluconazole. Two amino acid alterations reported to correspond to high MIC values of echinocandin, namely, F621I (F641) and S625L (S645), were found in the hot spot 1 region of FKS1. In addition, one new amino acid alteration, I1348S (I1368), was found outside of the FKS1 hot spot 2 region, and its contribution to echinocandin resistance requires future investigation. Diutina catenulata mainly infects patients with a weak immune system, and the high MIC values for various antifungals exhibited by these isolates may represent a challenge to clinical treatment.
| S-EPMC8586209 | biostudies-literature
Project description:Lomentospora prolificans is an opportunistic fungal pathogen with low susceptibility to current antifungal drugs. Here, we tested the in vitro susceptibility of 8 drugs against 42 clinical L. prolificans isolates. All isolates showed high MICs to voriconazole (MIC90>16 μg/ml), itraconazole (MIC90>16 μg/ml), posaconazole (MIC90>16 μg/ml), isavuconazole (MIC90>16 μg/ml), amphotericin B (MIC90>16 μg/ml), and terbinafine (MIC90>64 μg/ml) and high minimum effective concentrations (MECs) to micafungin (MEC90>8 μg/ml), with the exception of miltefosine showing an MIC90 value of 4 μg/ml. We examined six different in vitro drug combinations and found that the combination of voriconazole and terbinafine achieved the most synergistic effort against L. prolificans We then annotated the L. prolificans whole genome and located its Cyp51 and Fks1 genes. We completely sequenced the two genes to determine if any mutation would be related to azole and echinocandin resistance in L. prolificans We found no amino acid changes in Cyp51 protein and no tandem repeats in the 5' upstream region of the Cyp51 gene. However, we identified three intrinsic amino acid residues (G138S, M220I, and T289A) in the Cyp51 protein that were linked to azole resistance. Likewise, two intrinsic amino acid residues (F639Y, W695F) that have reported to confer echinocandin resistance were found in Fks1 hot spot regions. In addition, three new amino acid alterations (D440A, S634R, and H1245R) were found outside Fks1 hot spot regions, and their contributions to echinocandin resistance need future investigation. Overall, our findings support the notion that L. prolificans is intrinsically resistant to azoles and echinocandins.
| S-EPMC7577128 | biostudies-literature
Project description:Candida duobushaemulonii, type II Candida haemulonii complex, is closely related to Candida auris and capable of causing invasive and non-invasive infections in humans. Eleven strains of C. duobushaemulonii were collected from China Hospital Invasive Fungal Surveillance Net (CHIF-NET) and identified using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF), VITEK 2 Yeast Identification Card (YST), and internal transcribed spacer (ITS) sequencing. Whole genome sequencing of C. duobushaemulonii was done to determine their genotypes. Furthermore, C. duobushaemulonii strains were tested by Sensititre YeastOne™ and Clinical and Laboratory Institute (CLSI) broth microdilution panel for antifungal susceptibility. Three C. duobushaemulonii could not be identified by VITEK 2. All 11 isolates had high minimum inhibitory concentrations (MICs) to amphotericin B more than 2 μg/ml. One isolate showed a high MIC value of ≥64 μg/ml to 5-flucytosine. All isolates were wild type (WT) for triazoles and echinocandins. FUR1 variation may result in C. duobushaemulonii with high MIC to 5-flucytosine. Candida duobushaemulonii mainly infects patients with weakened immunity, and the amphotericin B resistance of these isolates might represent a challenge to clinical treatment.
| S-EPMC9760970 | biostudies-literature
Project description:Diutina catenulata Genome sequencing and assembly
| PRJNA1106016 | ENA
Project description:Fusarium spp. are fungal pathogens of humans and plants. Fusarium oxysporum and Fusarium solani are important species isolated from infections such as onychomycosis, fungal keratitis, invasive infections, and disseminated diseases. These pathologies have a very difficult therapeutic management and poor therapeutic responses, especially in patients with disseminated infection. Little information is available regarding the molecular mechanisms responsible for antifungal resistance in these fungi. methods: In this study, we performed a quantitative analysis of the transcriptional profile of F. oxysporum and F. solani, challenged with amphotericin B (AMB) and posaconazole (PSC) using RNA-seq. Quantitative real-time reverse transcription PCR (qRT-PCR) was used to validate the results results: Several genes related to mechanisms of antifungal resistance such as efflux pumps, ergosterol pathway synthesis, and responses to oxidative stress were found. Genes such as ERG11, ERG5, the Major Facilitator Superfamily (MFS), thioredoxin, and different dehydrogenase genes may explain the reduced susceptibility of Fusarium spp. against azoles and the possible mechanisms that may play an important role in induced resistance against polyenes. conclusions: Important differences in the levels of transcriptional expression were found between F. oxysporum and F. solani exposed to the two different antifungal treatments. Knowledge on the gene expression profiles and gene regulatory networks in Fusarium spp. during exposure to antifungal compounds, may help to identify possible molecular targets for the development of novel, better, and more specific therapeutic compounds. profile transcriptional of Fusarium spp changed to antifungal treatments in vitro
2016-06-01 | E-GEOD-82060 | biostudies-arrayexpress
Project description:Fusarium spp. are fungal pathogens of humans and plants. Fusarium oxysporum and Fusarium solani are important species isolated from infections such as onychomycosis, fungal keratitis, invasive infections, and disseminated diseases. These pathologies have a very difficult therapeutic management and poor therapeutic responses, especially in patients with disseminated infection. Little information is available regarding the molecular mechanisms responsible for antifungal resistance in these fungi. methods: In this study, we performed a quantitative analysis of the transcriptional profile of F. oxysporum and F. solani, challenged with amphotericin B (AMB) and posaconazole (PSC) using RNA-seq. Quantitative real-time reverse transcription PCR (qRT-PCR) was used to validate the results results: Several genes related to mechanisms of antifungal resistance such as efflux pumps, ergosterol pathway synthesis, and responses to oxidative stress were found. Genes such as ERG11, ERG5, the Major Facilitator Superfamily (MFS), thioredoxin, and different dehydrogenase genes may explain the reduced susceptibility of Fusarium spp. against azoles and the possible mechanisms that may play an important role in induced resistance against polyenes. conclusions: Important differences in the levels of transcriptional expression were found between F. oxysporum and F. solani exposed to the two different antifungal treatments. Knowledge on the gene expression profiles and gene regulatory networks in Fusarium spp. during exposure to antifungal compounds, may help to identify possible molecular targets for the development of novel, better, and more specific therapeutic compounds.
2016-06-01 | GSE82060 | GEO
Project description:The present study describes a novel mechanism of antifungal resistance affecting the susceptibility of both the azole and echinocandin antifungals in an azole-resistant isolate from a matched pair of C. parapsilosis isolates obtained from a patient with prosthetic valve endocarditis. Transcriptome analysis indicated differential expression of several genes in the resistant isolate including upregulation of ERG1, ERG2, ERG5, ERG6, ERG11, ERG24, ERG25, ERG27, DAP1 and UPC2, of the ergosterol biosynthesis pathway. Whole genome sequencing revealed a mutation in the ERG3 gene leading to a G111R amino acid substitution in the resistant isolate. Subsequent introduction of this allele in the native ERG3 locus in the susceptible isolate resulted in a fluconazole MIC of >64 mg/ml and a caspofungin MIC of 8 mg/ml. Corresponding allelic replacement of the wildtype allele for the mutant allele in the resistant isolate resulted in a drop in MIC to 1 mg/ml for both fluconazole and caspofungin. Sterol profiles indicated a loss of sterol demethylase activity as a result of this mutation. This work demonstrate that this G111R mutation is wholly responsible for the resistant phenotype in the C. parapsilosis resistant isolate and is the first report of this multidrug resistance mechanism.
2017-05-25 | GSE98986 | GEO