The minimum inhibitory concentration (MIC) of echinocandins against spp. does not represent the actual inhibition threshold of echinocandins. Therefore, the recommended method to evaluate their activity is determining the minimum effective concentration (MEC) in broth microdilution, a method that is less common in clinical settings.
View Article and Find Full Text PDFis a cariogenic bacterium in the oral cavity involved in plaque formation and dental caries. The endocannabinoid anandamide (AEA), a naturally occurring bioactive lipid, has been shown to have anti-bacterial and anti-biofilm activities against . We aimed here to study its effects on viability, biofilm formation and extracellular polysaccharide substance (EPS) production.
View Article and Find Full Text PDFDematiaceous fungi are pigmented molds with a high content of melanin in their cell walls that can cause fatal infections in immunocompromised hosts. Direct microscopy is the main method for the rapid diagnosis of dematiaceous fungi in clinical specimens. However, it is often difficult to distinguish their hyphae from non-dematiaceous hyphae and yeast pseudohyphae.
View Article and Find Full Text PDFA total of 476 European isolates (310 Cryptococcus neoformans var. grubii, 150 C. neoformans var.
View Article and Find Full Text PDFChanges in the interpretive-breakpoints for antifungals against various Candida species have raised the need to examine the significance of the phenomenon of the growth of microcolonies in agar diffusion inhibition zones, which has generally been considered negligible. The objective was to determine the incidence of cases in which microcolonies demonstrate fluconazole resistance according to current interpretive-breakpoints and whether their growth is associated with therapeutic failure. The fluconazole minimum inhibitory concentrations (MICs) of 100 blood culture isolates of Candida were performed by E-test on Roswell Park Memorial Institute (RPMI) agar and examined for the appearance of microcolonies.
View Article and Find Full Text PDFBiofilm formation by microorganisms depends on their communication by quorum sensing, which is mediated by small diffusible signaling molecules that accumulate in the extracellular environment. During human infection, the pathogenic yeast can form biofilm on medical devices, which protects the organism and increases its resistance to antifungal agents. The aim of this study was to test two novel heterocyclic compounds, S-8 (thiazolidinedione derivative, TZD) and NA-8 (succinimide derivative, SI), for their anti-biofilm activity against strains of and .
View Article and Find Full Text PDFFundamental niche prediction of Cryptococcus neoformans and Cryptococcus gattii in Europe is an important tool to understand where these pathogenic yeasts have a high probability to survive in the environment and therefore to identify the areas with high risk of infection. In this study, occurrence data for C. neoformans and C.
View Article and Find Full Text PDFCryptococcosis is a major fungal disease caused by members of the and species complexes. After more than 15 years of molecular genetic and phenotypic studies and much debate, a proposal for a taxonomic revision was made. The two varieties within were raised to species level, and the same was done for five genotypes within .
View Article and Find Full Text PDFIn order to elucidate the distribution of Cryptococcus neoformans and C. gattii in the Mediterranean basin, an extensive environmental survey was carried out during 2012-2015. A total of 302 sites located in 12 countries were sampled, 6436 samples from 3765 trees were collected and 5% of trees were found to be colonized by cryptococcal yeasts.
View Article and Find Full Text PDFThe purpose of this paper was to investigate the aggregation of amphotericin B (AMB) and AMB-arabinogalactan conjugate (AMB-AGC), and the interactions of these drugs with free and membrane-embedded sterols. Aggregation of AMB and AMB-AGC was studied by circular dichroic (CD) and UV absorbance spectroscopic techniques. The effect of liposomes on the spectra was utilized to investigate the interactions of aggregates with membrane-embedded sterols.
View Article and Find Full Text PDFBackground: Despite the increase in fungal isolates, the significance of chronic Candida albicans airway colonization in CF is unclear.
Aim: To investigate the impact of C. albicans airway colonization on CF disease severity.
Phylogenetic analysis of 11 genetic loci and results from many genotyping studies revealed significant genetic diversity with the pathogenic Cryptococcus gattii/Cryptococcus neoformans species complex. Genealogical concordance, coalescence-based, and species tree approaches supported the presence of distinct and concordant lineages within the complex. Consequently, we propose to recognize the current C.
View Article and Find Full Text PDFThe fungal meningitis pathogen Cryptococcus neoformans is a central driver of mortality in HIV/AIDS. We report a genome-scale chemical genetic data map for this pathogen that quantifies the impact of 439 small-molecule challenges on 1,448 gene knockouts. We identified chemical phenotypes for 83% of mutants screened and at least one genetic response for each compound.
View Article and Find Full Text PDFAmphotericin B (AMB) arabinogalactan (AG) conjugate was synthesized by the conjugation of AMB to oxidized AG by reductive amination. The conjugate was evaluated for in vitro antifungal activity and in vivo toxicity. Optimization of the conjugation process was investigated using large batches of 100 g, which are 20 times larger than previously reported for AMB-AG conjugation.
View Article and Find Full Text PDFJ Antimicrob Chemother
February 2014
Objectives: The aims of this study were to develop new anti-biofilm drugs, examine their activity against Candida albicans biofilm and investigate their structure-activity relationship and mechanism of action.
Methods: A series of thiazolidinedione and succinimide derivatives were synthesized and their ability to inhibit C. albicans biofilm formation and destroy pre-formed biofilm was tested.
Over the past two decades, several fungal outbreaks have occurred, including the high-profile 'Vancouver Island' and 'Pacific Northwest' outbreaks, caused by Cryptococcus gattii, which has affected hundreds of otherwise healthy humans and animals. Over the same time period, C. gattii was the cause of several additional case clusters at localities outside of the tropical and subtropical climate zones where the species normally occurs.
View Article and Find Full Text PDFA novel lipid formulation of Nystatin (NYT), Nystatin-Intralipid (NYT-IL), which was found to be more active and less toxic in vitro and in vivo, was developed in our laboratory. The aim of the present study was to explore the possible mechanisms underlying its biological activity. To assess mechanisms affecting fungal cells we conducted the following experiments: killing kinetics, scanning and transmission electron microscopy (EM), measurements of potassium ion leakage and susceptibility in the presence of ergosterol.
View Article and Find Full Text PDFAntimicrob Agents Chemother
November 2012
Amphotericin B (AMB) is an effective antifungal agent. However, its therapeutic use is hampered by its toxicity, mainly due to channel formation across kidney cell membranes and the disruption of postendocytic trafficking. We previously described a safe injectable AMB-arabinogalactan (AG) conjugate with neutralized toxicity.
View Article and Find Full Text PDFObjectives: We developed a novel lipid formulation of nystatin suitable for parenteral administration, nystatin-intralipid (NYT-IL), with antifungal activity and reduced toxicity in mice. We investigated the pharmacokinetics, tissue distribution and immunomodulatory effect of NYT-IL in mice.
Methods: Nystatin levels in serum and organs were determined using HPLC after NYT-IL or nystatin administration in mice.
Int J Pediatr Otorhinolaryngol
July 2011
Objective: Acute invasive fungal sinusitis (AIFS) appears mainly in immunocompromized patients and may be caused by various pathogens. We describe a teenager with invasive sinonasal Scopulariopsis brevicaulis and review all the reports on this rare pathogen.
Methods: A literature search on Scopulariopsis sinonasal invasive infections was performed and clinical data including age, gender, co-morbidities, treatment and prognosis was collected on all the patients.
Conjugation of poorly soluble drugs to polysaccharides affects their solubility, pharmacokinetics (PK), and pharmacodynamics. The need for amphotericin B (AmB) analog with improved solubility and reduced toxicity is immense. Conjugation of AmB to arabinogalactan (AG) produced a highly soluble AmB-AG conjugate, with high and low molecular weight (H-M(w) and L-M(w)) fractions.
View Article and Find Full Text PDFIn 1999, the population of Vancouver Island, Canada, began to experience an outbreak of a fatal fungal disease caused by a highly virulent lineage of Cryptococcus gattii. This organism has recently spread to the Canadian mainland and Pacific Northwest, but the molecular cause of the outbreak remains unknown. Here we show that the Vancouver Island outbreak (VIO) isolates have dramatically increased their ability to replicate within macrophages of the mammalian immune system in comparison with other C.
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