A5064137145- Fungal Infections and Studies
- Antifungal resistance and susceptibility
- Sphingolipid Metabolism and Signaling
- Toxin Mechanisms and Immunotoxins
- Nail Diseases and Treatments
- Plant-Microbe Interactions and Immunity
- Lipid Membrane Structure and Behavior
- Carbohydrate Chemistry and Synthesis
- Polysaccharides and Plant Cell Walls
- Fungal and yeast genetics research
- Phytoplasmas and Hemiptera pathogens
- Streptococcal Infections and Treatments
- Fungal Biology and Applications
- Cellular transport and secretion
- Infectious Diseases and Mycology
- Synthesis and Biological Evaluation
- Microbial Natural Products and Biosynthesis
- Research on Leishmaniasis Studies
- Peptidase Inhibition and Analysis
- Plant Disease Resistance and Genetics
- Cytomegalovirus and herpesvirus research
- Synthesis and biological activity
- Signaling Pathways in Disease
- Plant Pathogens and Fungal Diseases
- Pneumocystis jirovecii pneumonia detection and treatment
Stony Brook University
2015-2024
Northport VA Medical Center
2016-2024
Stony Brook School
2024
State University of New York
2023
The University of Texas Southwestern Medical Center
2022
McGill University Health Centre
2022
Munich Cluster for Systems Neurology
2022
Technical University of Munich
2022
University of California, San Francisco
2022
Novartis (India)
2022
ABSTRACT Azoles target the ergosterol biosynthetic enzyme lanosterol 14α-demethylase and are a widely applied class of antifungal agents because their broad therapeutic window, wide spectrum activity, low toxicity. Unfortunately, azoles generally fungistatic resistance to fluconazole is emerging in several fungal pathogens. We recently established that protein phosphatase calcineurin allows survival Candida albicans during membrane stress exerted by azoles. The inhibitors cyclosporine A...
ABSTRACT Twenty analogues of pentamidine, 7 primary metabolites and 30 dicationic substituted bis-benzimidazoles were screened for their inhibitory fungicidal activities against Candida albicans Cryptococcus neoformans . A majority the compounds had MICs at which 80% strains inhibited (MIC 80 s) comparable to those amphotericin B fluconazole. Unlike fluconazole, many these found have potent activity. The most compound C. an MIC ≤0.09 μg/ml, 0.19 μg/ml. Selected also be active Aspergillus...
Recent estimates suggest that >300 million people are afflicted by serious fungal infections worldwide. Current antifungal drugs static and toxic and/or have a narrow spectrum of activity. Thus, there is an urgent need for the development new drugs. The sphingolipid glucosylceramide (GlcCer) critical in promoting virulence variety human-pathogenic fungi. In this study, we screened synthetic drug library compounds target synthesis fungal, but not mammalian, GlcCer found two...
There is an urgent need to identify the cellular and molecular mechanisms responsible for severe COVID-19 that results in death. We initially performed both untargeted targeted lipidomics as well focused biochemical analyses of 127 plasma samples found elevated metabolites associated with secreted phospholipase A2 (sPLA2) activity mitochondrial dysfunction patients COVID-19. Deceased had higher levels circulating, catalytically active sPLA2 group IIA (sPLA2-IIA), a median value was 9.6-fold...
The number of deaths from cryptococcal meningitis is around 180,000 per year. disease the second leading cause mortality among individuals with AIDS. Antifungal treatment costly and associated adverse effects resistance, evidencing urgency development both therapeutic prophylactic tools. Here we demonstrate key roles polysaccharide- glycolipid-containing structures in a vaccination model to prevent cryptococcosis.
The ability to undergo morphological changes during adaptation distinct environments is exploited by Candida albicans and has a direct impact on biofilm formation virulence. Morphogenesis controlled diversity of stimuli, including osmotic stress, pH, starvation, presence serum, microbial components, among others.
Cryptococcus neoformans is an opportunistic fungal pathogen that causes life-threatening infections of the central nervous system. Existing therapies include amphotericin B, fluconazole, and flucytosine, which are limited by toxic side effects emergence drug resistance. We recently demonstrated protein phosphatase calcineurin required for growth at 37 degrees C virulence C. neoformans. Because target potent inhibitors in widespread clinical use, cyclosporine FK506 (tacrolimus), it attractive...
The in vitro activity of the new antifungal drug pneumocandin L-743,872 against 55 isolates clinically important molds was examined by an adapted macrobroth dilution method for yeasts. Pneumocandin exhibited Alternaria sp., Aspergillus flavus, fumigatus, Curvularia lunata, Exophiala jeanselmei, Fonsecaea pedrosoi, Paecilomyces variotii, and Scedosporium apiospermum. appeared to lack significant inhibitory Fusarium oxysporum, solani, Rhizopus arrhizus, lilacinus, prolificans.
ABSTRACT Candida albicans and Cryptococcus neoformans cause both superficial disseminated infections in humans. Current antifungal therapies for deep-seated are limited to amphotericin B, flucytosine, azoles. A limitation is that commonly used azoles fungistatic vitro vivo. Our studies address the mechanisms of activity immunosuppressive drug rapamycin (sirolimus) its analogs with decreased activity. C. rbp1/rbp1 mutant strains lacking a homolog FK506-rapamycin target protein FKBP12 were...
The immunosuppressant FK506 (tacrolimus) is an antifungal natural product macrolide that suppresses the immune system by blocking T-cell activation. In complex with intracellular protein FKBP12, inhibits calcineurin, a Ca(2+)-calmodulin-dependent serine-threonine phosphatase. We recently reported growth of opportunistic fungal pathogen Cryptococcus neoformans resistant to at 24 degrees C but sensitive 37 and target FKBP12-FK506, required for in vitro pathogenicity vivo. These findings...
Cryptococcus neoformans is a fungal pathogen that, after inhalation, can disseminate to the brain. Host alveolar macrophages (AMs) represent first defense against fungus. Once phagocytosed by AMs, cells are killed concerted mechanism, involving host-cellular response. If cellular response impaired, phagocytosis of fungus may be detrimental for host, since C. grow within macrophages. Here, we identified novel cryptococcal gene encoding antiphagocytic protein 1 (App1). App1 cytoplasmic that...
Cryptococcus neoformans is a leading cause of life-threatening fungal infection in immunocompromised patients. Inositol-phosphoryl ceramide synthase 1 (Ipc1) fungus-specific enzyme, encoded by the essential IPC1 gene, that catalyzes formation complex sphingolipids and may also regulate levels phytoceramide diacylglycerol. Here, we investigated functions this gene modulating its expression C. using galactose-inducible promoter. Down-regulation significantly lowers certain virulence traits...
ABSTRACT In previous studies we showed that a Cryptococcus neoformans mutant lacking glucosylceramide (Δ gcs1 ) is avirulent and unable to reach the brain when it administered intranasally into an immunocompetent mouse contained in lung granuloma. To determine whether granuloma formation key for containment of C. Δ , studied role T- NK-cell-immunodeficient model (Tgε26) which alveolar macrophages (AMs) are not activated expected. The results show Tgε26 mice infected with do produce...
ABSTRACT In recent years, sphingolipids have emerged as critical molecules in the regulation of microbial pathogenesis. fungi, synthesis complex is important for pathogenicity, but role sphingolipid degradation fungal virulence not known. Here, we isolated and characterized inositol phosphosphingolipid-phospholipase C1 ( ISC1 ) gene from pathogen Cryptococcus neoformans showed that it encodes an enzyme metabolizes sphingolipids. Isc1 protects C. acidic, oxidative, nitrosative stresses, which...
Cryptococcus species cause invasive infections in humans. Lipids play an important role the progression of these infections. Independent studies done by our group and others provide some detail about functions lipids However, pathways biosynthesis metabolism are not completely understood. To thoroughly understand physiological lipids, a proper structure composition analysis is demanded. In this study, detailed spectroscopic lipid extracts from gattii grubii strains presented. Sphingolipid...
Cryptococcosis caused by Cryptococcus neoformans and gattii affects a large population is cause of significant morbidity mortality. Despite its public health burden, there are currently no vaccines against cryptococcosis new strategies such infections needed. In this study, we demonstrate that C. has the biochemical ability to metabolize sterylglucosides (SGs), class immunomodulatory glycolipids. Genetic manipulations eliminate cryptococccal sterylglucosidase lead accumulation SGs generate...