Browse
Submit Data
Databases
API
Help

Dataset Information

24 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Acquired echinocandin resistance in a Candida krusei isolate due to modification of glucan synthase.

ABSTRACT: A Candida krusei strain from a patient with acute myelogenous leukemia that displayed reduced susceptibility to echinocandin drugs contained a heterozygous mutation, T2080K, in FKS1. The resulting Phe655-->Cys substitution altered the sensitivity of glucan synthase to echinocandin drugs, consistent with a common mechanism for echinocandin resistance in Candida spp.

SUBMITTER: Kahn JN

PROVIDER: S-EPMC1855530 | biostudies-literature | 2007 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Acquired echinocandin resistance in a Candida krusei isolate due to modification of glucan synthase.

Kahn Jennifer Nielsen JN Garcia-Effron Guillermo G Hsu Ming-Jo MJ Park Steven S Marr Kieren A KA Perlin David S DS

Antimicrobial agents and chemotherapy 20070226 5

A Candida krusei strain from a patient with acute myelogenous leukemia that displayed reduced susceptibility to echinocandin drugs contained a heterozygous mutation, T2080K, in FKS1. The resulting Phe655-->Cys substitution altered the sensitivity of glucan synthase to echinocandin drugs, consistent with a common mechanism for echinocandin resistance in Candida spp. ...[more]

PMID: 17325225

Similar Datasets

Rapid development of Candida krusei echinocandin resistance during caspofungin therapy.

Project description:In invasive candidiasis, there has been an epidemiological shift from Candida albicans to non-albicans species infections, including infections with C. glabrata, C. parapsilosis, C. tropicalis, and C. krusei. Although the prevalence of C. krusei remains low among yeast infections, its intrinsic resistance to fluconazole raises epidemiological and therapeutic concerns. Echinocandins have in vitro activity against most Candida spp. and are the first-line agents in the treatment of candidemia. Although resistance to echinocandin drugs is still rare, individual cases of C. krusei resistance have been reported in recent years, especially with strains that have been under selective pressure. A total of 15 C. krusei strains, isolated from the blood, urine, and soft tissue of an acute lymphocytic leukemia patient, were analyzed. Strains developed echinocandin resistance during 10 days of caspofungin therapy. The molecular epidemiology of the isolates was investigated using two different typing methods: PCR-based amplification of the species-specific repetitive polymorphic CKRS-1 sequence and multilocus sequence typing. All isolates were genetically related, and the mechanism involved in decreased echinocandin susceptibility was characterized. Clinical resistance was associated with an increase in echinocandin MICs in vitro and was related to three different mutations in hot spot 1 of the target enzyme Fks1p. Molecular evidence of the rapid acquisition of resistance by different mutations in FKS1 highlights the need to monitor the development of resistance in C. krusei infections treated with echinocandin drugs.

| S-EPMC4604417 | biostudies-literature

Echinocandin failure case due to a previously unreported FKS1 mutation in Candida krusei.

Project description:Echinocandins are the preferred therapy for invasive infections due to Candida krusei. We present here a case of clinical failure involving C. krusei with a characteristic FKS1 hot spot mutation not previously reported in C. krusei that was isolated after 14 days of treatment. Anidulafungin MICs were elevated by ≥ 5 dilution steps above the clinical breakpoint but by only 1 step for a Candida albicans isolate harboring the corresponding mutation, suggesting a notable species-specific difference in the MIC increase conferred by this mutation.

| S-EPMC4068455 | biostudies-literature

Prevalence of Antifungal Resistance, Genetic Basis of Acquired Azole and Echinocandin Resistance, and Genotyping of Candida krusei Recovered from an International Collection.

Project description:This study was designed to evaluate the prevalence of antifungal resistance, genetic mechanisms associated with in vitro induction of azole and echinocandin resistance and genotyping of Candida krusei, which is intrinsically resistant to fluconazole and is recovered from clinical and nonclinical sources from different countries. Our results indicated that all the isolates were susceptible or had the wild phenotype (WT) to azoles, amphotericin B, and only 1.27% showed non-WT for flucytosine. Although 70.88% of the isolates were resistant to caspofungin, none of them were categorized as echinocandin-resistant as all were susceptible to micafungin and no FKS1 hot spot 1 (HS1) or HS2 mutations were detected. In vitro induction of azole and echinocandin resistance confirmed the rapid development of resistance at low concentrations of fluconazole (4 μg/ml), voriconazole (0.06 μg/ml), and micafungin (0.03 μg/ml), with no difference between clinical and nonclinical isolates in the resistance development. Overexpression of ABC1 gene and FKS1 HS1 mutations were the major mechanisms responsible for azole and echinocandin resistance, respectively. Genotyping of our 79 isolates coupled with 217 other isolates from different sources and geography confirmed that the isolates belong to two main subpopulations, with isolates from human clinical material and Asia being more predominant in cluster 1, and environmental and animals isolates and those from Europe in cluster 2. Our results are of critical concern, since realizing that the C. krusei resistance mechanisms and their genotyping are crucial for guiding specific therapy and for exploring the potential infection source.

| S-EPMC8846461 | biostudies-literature

Recurrent episodes of Candidemia due to Candida glabrata, Candida tropicalis and Candida albicans with acquired echinocandin resistance.

Project description:Mixed fungal infection and acquired echinocandin resistance of Candida spp. remain infrequent. In this study we have reported the case of a patient hospitalized for tuberculosis who experienced multiple infections due to three common Candida species (C. albicans, C. glabrata, C. tropicalis). Furthermore, consecutive isolates from blood cultures and heart valve were found resistant to azoles (C. tropicalis) and to echinocandin with either novel (C. tropicalis) or previously described (C. albicans) missense mutations in the Fks gene.

| S-EPMC5155041 | biostudies-literature

Novel Non-Hot Spot Modification in Fks1 of Candida auris Confers Echinocandin Resistance.

Project description:We determined the echinocandin susceptibility and FKS1 genotypes of 13 clinical isolates of Candida auris that were recovered from 4 patients at a tertiary care center in Salvador, Brazil. Three isolates were categorized as echinocandin-resistant, and they harbored a novel FKS1 mutation that led to an amino acid change W691L located downstream from hot spot 1. When introduced to echinocandin-susceptible C. auris strains by CRISPR/Cas9, Fks1 W691L induced elevated MIC values to all echinocandins (anidulafungin, 16 to 32×; caspofungin, >64×; micafungin, >64×).

| S-EPMC10269051 | biostudies-literature

Emergence of a Candida krusei isolate with reduced susceptibility to caspofungin during therapy.

Project description:Clinical failure associated with reduced susceptibility to caspofungin has been described in Candida albicans and C. parapsilosis. We report a case of Candida krusei infection that progressed despite caspofungin therapy. Reduced microbial susceptibility to all three echinocandins (caspofungin, anidulafungin, and micafungin) was noted but was not associated with mutations in FKS1.

| S-EPMC1489805 | biostudies-literature

Multilaboratory testing of antifungal combinations against a quality control isolate of Candida krusei.

Project description:Candida krusei ATCC 6258 was tested by eight laboratories using 96-well plates containing checkerboard pairwise combinations of amphotericin B (AMB), posaconazole (PSC), caspofungin (CSP), and voriconazole (VRC). The methodology led to reproducible results across the laboratories. All drug combinations yielded MICs lower than the MICs of any two drugs tested singly, and combinations of AMB, PSC, CSP, and VRC were indifferent (no antagonism) by summations of fractional inhibitory concentration.

| S-EPMC2292538 | biostudies-literature

Genomic description of acquired fluconazole- and echinocandin-resistance in patients with serial Candida glabrata isolates.

Project description:Candida glabrata is one of the most common causes of systemic candidiasis, often resistant to antifungal medications. To describe the genomic context of emerging resistance, we conducted a retrospective analysis of 82 serially collected isolates from 33 patients from population-based candidemia surveillance in the United States. We used whole-genome sequencing to determine the genetic relationships between isolates obtained from the same patient. Phylogenetic analysis demonstrated that isolates from 29 patients were clustered by patient. The median SNPs between isolates from the same patient was 30 (range: 7-96 SNPs), while unrelated strains infected four patients. Twenty-one isolates were resistant to echinocandins, and 24 were resistant to fluconazole. All echinocandin-resistant isolates carried a mutation either in the FKS1 or FKS2 HS1 region. Of the 24 fluconazole-resistant isolates, 17 (71%) had non-synonymous polymorphisms in the PDR1 gene, which were absent in susceptible isolates. In 11 patients, a genetically related resistant isolate was collected after recovering susceptible isolates, indicating in vivo acquisition of resistance. These findings allowed us to estimate the intra-host diversity of C. glabrata and propose an upper boundary of 96 SNPs for defining genetically related isolates, which can be used to assess donor-to-host transmission, nosocomial transmission, or acquired resistance. IMPORTANCE In our study, mutations associated to azole resistance and echinocandin resistance were detected in Candida glabrata isolates using a whole-genome sequence. C. glabrata is the second most common cause of candidemia in the United States, which rapidly acquires resistance to antifungals, in vitro and in vivo.

| S-EPMC10865870 | biostudies-literature

Echinocandin Resistance in Candida auris Occurs in the Murine Gastrointestinal Tract Due to FKS1 Mutations.

Project description:Candida auris is resistant to multiple antifungal agents. This study investigated its antifungal susceptibility and explored FKS1 mutations across the isolates from mice enterically colonized with wild-type C. auris and treated with echinocandin. Resistant C. auris with FKS1 mutations, including S639F, S639Y, D642Y, R1354H, or R1354Y, were isolated and found to be micafungin- and caspofungin-resistant in vivo; however, the MICs of isolates with mutation in R1354 remained below the micafungin breakpoint in vitro.

| S-EPMC10112215 | biostudies-literature

Whole Genome Sequence of the Heterozygous Clinical Isolate Candida krusei 81-B-5.

Project description:Candida krusei is a diploid, heterozygous yeast that is an opportunistic fungal pathogen in immunocompromised patients. This species also is utilized for fermenting cocoa beans during chocolate production. One major concern in the clinical setting is the innate resistance of this species to the most commonly used antifungal drug fluconazole. Here, we report a high-quality genome sequence and assembly for the first clinical isolate of C. krusei, strain 81-B-5, into 11 scaffolds generated with PacBio sequencing technology. Gene annotation and comparative analysis revealed a unique profile of transporters that could play a role in drug resistance or adaptation to different environments. In addition, we show that, while 82% of the genome is highly heterozygous, a 2.0 Mb region of the largest scaffold has undergone loss of heterozygosity. This genome will serve as a reference for further genetic studies of this pathogen.

| S-EPMC5592916 | biostudies-literature

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