A5016729618- Antifungal resistance and susceptibility
- Fungal Infections and Studies
- Plant Pathogens and Fungal Diseases
- Nail Diseases and Treatments
- Infectious Diseases and Mycology
- Fungal Biology and Applications
- Pneumocystis jirovecii pneumonia detection and treatment
- Peptidase Inhibition and Analysis
- Mycotoxins in Agriculture and Food
- Antimicrobial Resistance in Staphylococcus
- Nematode management and characterization studies
- Microbial Natural Products and Biosynthesis
- Helminth infection and control
- Synthesis and Biological Evaluation
- Mycobacterium research and diagnosis
- Reproductive tract infections research
- Insects and Parasite Interactions
- Molecular Biology Techniques and Applications
- Brucella: diagnosis, epidemiology, treatment
- Entomopathogenic Microorganisms in Pest Control
- Science, Technology, and Education in Latin America
- Burkholderia infections and melioidosis
- Actinomycetales infections and treatment
- Cancer-related gene regulation
- Parasitic Diseases Research and Treatment
Centro Científico Tecnológico - Santa Fe
2016-2025
National University of the Littoral
2016-2025
Consejo Nacional de Investigaciones Científicas y Técnicas
2013-2024
Centro Científico Tecnológico - San Juan
2020-2022
Centro Científico Tecnológico - Tucumán
2015
Rutgers New Jersey Medical School
2007-2012
International Center for Public Health
2008-2012
Hospital Universitario 12 De Octubre
2006-2009
Rutgers, The State University of New Jersey
2008
Centro Nacional de Microbiologia
2004-2007
ABSTRACT Fourteen Aspergillus fumigatus clinical isolates that exhibited a pattern of reduced susceptibility to triazole drugs were analyzed. The sequences the cyp51A gene from all showed presence point mutation at t364a, which led substitution leucine 98 for histidine (L98H), together with two copies 34-bp sequence in tandem promoter gene. Quantitative expression analysis (real-time PCR) up an eightfold increase level compared by susceptible strain. Three PCR fragments one azole-resistant...
Thirteen Candida glabrata strains harboring a range of mutations in hot spot regions FKS1 and FKS2 were studied. The linked to an echinocandin reduced susceptibility phenotype. Sequence alignments showed that 11 out the 13 mutants harbored mutation or not previously implicated C. glabrata. A detailed kinetic characterization demonstrated amino acid substitutions Fks1p Fks2p drug sensitivity mutant 1,3-beta-D-glucan synthase by 2 3 log orders relative wild-type enzyme. These also found reduce...
Candida parapsilosis has emerged as a common cause of invasive fungal infection, especially in Latin America and the neonatal setting. C. is part closely related group organisms that includes species orthopsilosis metapsilosis. All three show elevated MICs for new echinocandin class drugs caspofungin, micafungin, anidulafungin relative to other species. Despite potential impacts on therapy, mechanism behind this reduced susceptibility not been determined. In report, we investigated role...
A detailed kinetic characterization of echinocandin inhibition was performed for mutant 1,3-beta-d-glucan synthase enzymes from clinical isolates Candida albicans with nine different FKS1 mutations resulting in high MICs. Among 14 Fks1p studied, the parameters 50% inhibitory concentration and K(i) increased 50-fold to several thousandfold relative those wild type. Enzymes at Ser645 (S645P, S645Y, S645F) within hot spot 1 showed most prominent decrease sensitivity, while N- C-terminal ends...
Five clinical isolates of Aspergillus fumigatus that exhibited similar patterns reduced susceptibility to itraconazole and other triazole drugs were analyzed. Sequence analysis genes (cyp51A cyp51B) encoding the 14alpha-sterol demethylases revealed all five strains harbored mutations in cyp51A resulting replacement methionine at residue 220 by valine, lysine, or threonine. When mutated introduced into an A. wild-type strain, transformants agents, confirming responsible for resistance phenotype.
Ergosterol is an important constituent of fungal membranes. Azoles inhibit ergosterol biosynthesis, although the cellular basis for their antifungal activity not understood. We used multiple approaches to demonstrate a critical requirement in vacuolar H+-ATPase function, which known be essential virulence. biosynthesis mutants S. cerevisiae failed acidify vacuole and exhibited vma− phenotypes. Extraction from membranes also inactivated V-ATPase without disrupting membrane association its...
ABSTRACT For Candida species, a bimodal wild-type MIC distribution for echinocandins exists, but resistance to is rare. We characterized isolates from patients with invasive candidiasis (IC) breaking through ≥3 doses of micafungin therapy during the first 28 months its use at our center: MICs were determined and hot-spot regions within FKS genes sequenced. Eleven 12 breakthrough IC cases identified in transplant recipients. The median duration exposure prior was 33 days (range, 5 165)....
This study compared nine susceptibility testing methods and 12 endpoints for anidulafungin, caspofungin, micafungin with the same collection of blinded FKS hot spot mutant (n = 29) wild-type isolates 94). The tests included EUCAST Edef 7.1, agar dilution, Etest, disk diffusion RPMI-1640 plus 2% glucose (2G) IsoSensitest-2G media CLSI M27A-3. Microdilution plates were read after 24 48 h. following test parameters evaluated: fks mutants overlapping distribution, distance between two...
The identification of FKS1 mutations in Candida albicans associated with echinocandin resistance has raised concerns over the spread drug-resistant strains. We studied impact fks1 on C. virulence and fitness. Compared wild-type strains for FKS1, echinocandin-resistant homozygous hot-spot had reduced maximum catalytic capacity their glucan synthase complexes thicker cell walls attributable to increased wall chitin content. mutants highest contents growth rates impaired filamentation...
ABSTRACT Method-dependent Etest epidemiological cutoff values (ECVs) are not available for susceptibility testing of either Candida or Aspergillus species with amphotericin B echinocandins. In addition, reference caspofungin MICs spp. unreliable. and wild-type (WT) MIC distributions (microorganisms in a species-drug combination no detectable phenotypic resistance) were established 4,341 albicans , 113 C. dubliniensis 1,683 glabrata complex (SC), 709 krusei 767 parapsilosis SC, 796 tropicalis...
An S678P substitution in Fks1p, the major subunit of glucan synthase, was sufficient to confer echinocandin resistance Aspergillus fumigatus. The equivalent mutation Candida spp. has been implicated resistance. This work demonstrates that modification Fks1p is a conserved mechanism for pathogenic fungi.
We identified three cases of C. tropicalis strains causing breakthrough fungemia in allogeneic stem cell recipients receiving caspofungin prophylaxis and treatment. Three genetically unrelated isolates with high echinocandin MICs were identified. Each strain carried a characteristic mutation conferring an amino acid substitution within Fks1p hot spot 1.
The role of Aspergillus fumigatus 14alpha-sterol demethylase (Cyp51A) in azole drug susceptibility was assessed. Targeted disruption cyp51A azole-susceptible and -resistant strains decreased MICs from 2- to 40-fold. mutants were morphologically indistinguishable the wild-type strain, retaining ability cause pulmonary disease neutropenic mice.
Caspofungin is used for the treatment of acute invasive candidiasis and as salvage aspergillosis. We report characteristics isolates Candida albicans Aspergillus fumigatus detected in a patient with breakthrough infection complicating severe gastrointestinal surgery evaluate capability susceptibility methods to identify candin resistance. The C. caspofungin anidulafungin was investigated by Etest, microdilution (European Committee on Antibiotic Susceptibility Testing [EUCAST] CLSI), disk...
We describe a case of recurring Candida glabrata infection in 68-year-old African-American female on caspofungin therapy. The initial isolate was susceptible, but isolates recovered during following relapses were not. All clonal, and high-MIC strains contained mutation the highly conserved hot spot 1 region Fks1p.
ABSTRACT A Candida krusei strain from a patient with acute myelogenous leukemia that displayed reduced susceptibility to echinocandin drugs contained heterozygous mutation, T2080K, in FKS1 . The resulting Phe655→Cys substitution altered the sensitivity of glucan synthase drugs, consistent common mechanism for resistance spp.
Two clinical isolates of Aspergillus fumigatus, designated AT and DK, were recently obtained from patients failing caspofungin itraconazole therapy, respectively. The tested by microdilution for susceptibility to itraconazole, voriconazole, posaconazole, ravuconazole, Etest amphotericin B caspofungin. Susceptibility testing documented that the DK isolate was azole resistant (itraconazole posaconazole MICs, >4 microg/ml; voriconazole MIC, 2 ravuconazole 4 microg/ml), resistance confirmed in a...
Antifungal efficacies of the echinocandin drugs caspofungin, micafungin, and anidulafungin were reduced significantly in presence 50% human serum, which yielded nearly equivalent MICs or minimum effective concentrations against diverse Candida spp. Aspergillus Consistent with a direct drug interaction, serum decreased sensitivity glucan synthase to drugs.
Triazole resistance in Aspergillus fumigatus is an uncommon but rising phenomenon. Susceptibility testing rarely performed and can take 48 h or longer, which impediment to effective therapy. Molecular diagnostic probing of well-defined mechanisms, serve as surrogate markers, provides alternative approach rapidly (within hours) efficiently identify resistant strains. The mechanisms triazole A. are limited amino acid substitutions the drug target Cyp51A include at positions Gly 54, 138, Met...
We studied three clinical isolates of Candida spp. (one C. tropicalis isolate and two glabrata isolates) from patients with invasive candidiasis. The first emerged during echinocandin treatment, while the others after same treatment. These strains harbored an amino acid substitution in Fksp never linked before reduced susceptibility or glabrata. molecular mechanism was confirmed using a 1,3-beta-D-glucan synthase inhibition assay.
Aspergillus fumigatus intrinsic fluconazole resistance has been demonstrated to be linked the CYP51A gene, although precise molecular mechanism not elucidated yet. Comparisons between A. Cyp51Ap and Candida albicans Erg11p sequences showed differences in amino acid residues already associated with C. The aim of this study was analyze role natural polymorphism I301 phenotype pathogen. residue replaced a threonine (analogue T315 at fluconazole-susceptible Erg11p) by changing one single...
Although the Sensititre Yeast-One (SYO) and Etest methods are widely utilized, interpretive criteria not available for triazole susceptibility testing of Candida or Aspergillus species. We collected fluconazole, itraconazole, posaconazole, voriconazole SYO MICs from 39 laboratories representing all continents (method/agent-dependent) 11,171 albicans , 215 C. dubliniensis 4,418 glabrata species complex, 157 guilliermondii ( Meyerozyma ), 676 krusei Pichia kudriavzevii 298 lusitaniae...