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173 results on '"Wormley, Floyd L."'

2. Screening the medicine for malaria venture's Pandemic Response Box to identify novel inhibitors of Candida albicans and Candida auris biofilm formation.

Author

Ajetunmobi, Olabayo H., Chaturvedi, Ashok K., Badali, Hamid, Vaccaro, Alessandra, Najvar, Laura, Wormley, Floyd L., Wiederhold, Nathan P., Patterson, Thomas F., and Lopez‐Ribot, Jose L.

Subjects
CANDIDA albicans, MEDICAL screening, FILAMENTOUS fungi, BIOFILMS, MALARIA, PANDEMICS, ANTIFUNGAL agents, MICROBIAL fuel cells
Abstract

Candida spp. are opportunistic yeasts capable of forming biofilms, which contribute to resistance, increasing the urgency for new effective antifungal therapies. Repurposing existing drugs could significantly accelerate the development of novel therapies against candidiasis. We screened the Pandemic Response Box containing 400 diverse drug‐like molecules active against bacteria, viruses or fungi, for inhibitors of Candida albicans and Candida auris biofilm formation. Initial hits were identified based on the demonstration of >70% inhibitory activity. Dose–response assays were used to confirm the antifungal activity of initial hits and establish their potency. The spectrum of antifungal activity of the leading compounds was determined against a panel of medically important fungi, and the in vivo activity of the leading repositionable agent was evaluated in murine models of C. albicans and C. auris systemic candidiasis. The primary screening identified 20 hit compounds, and their antifungal activity and potency against C. albicans and C. auris were validated using dose–response measurements. From these experiments, the rapalog everolimus, emerged as the leading repositionable candidate. Everolimus displayed potent antifungal activity against different Candida spp., but more moderate levels of activity against filamentous fungi. Treatment with everolimus increased survival of mice infected with C. albicans, but not those with C. auris. The screening of the Pandemic Response Box resulted in the identification of several drugs with novel antifungal activity, with everolimus emerging as the main repositionable candidate. Further in vitro and in vivo studies are needed to confirm its potential therapeutic use. [ABSTRACT FROM AUTHOR]

Published
2023
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18. A Novel Mycovirus Evokes Transcriptional Rewiring in the Fungus Malassezia and Stimulates Beta Interferon Production in Macrophages

Author

Wormley, Floyd L, Wormley, F L ( Floyd L ), Applen Clancey, Shelly, Ruchti, Fiorella, LeibundGut-Landmann, Salomé; https://orcid.org/0000-0002-5724-4837, Heitman, Joseph, Ianiri, Giuseppe; https://orcid.org/0000-0002-3278-8678, Wormley, Floyd L, Wormley, F L ( Floyd L ), Applen Clancey, Shelly, Ruchti, Fiorella, LeibundGut-Landmann, Salomé; https://orcid.org/0000-0002-5724-4837, Heitman, Joseph, and Ianiri, Giuseppe; https://orcid.org/0000-0002-3278-8678

Abstract

Mycoviruses infect fungi, and while most persist asymptomatically, there are examples of mycoviruses having both beneficial and detrimental effects on their host. Virus-infected Saccharomyces and Ustilago strains exhibit a killer phenotype conferring a growth advantage over uninfected strains and other competing yeast species, whereas hypovirus-infected Cryphonectria parasitica displays defects in growth, sporulation, and virulence. In this study, we identify a double-stranded RNA (dsRNA) mycovirus in five Malassezia species. Sequence analysis reveals it to be a totivirus with two dsRNA segments: a larger 4.5-kb segment with genes encoding components for viral replication and maintenance, and a smaller 1.4-kb segment encoding a novel protein. Furthermore, transcriptome sequencing (RNA-seq) of virus-infected versus virus-cured Malassezia sympodialis revealed an upregulation of dozens of ribosomal components in the cell, suggesting the virus modifies the transcriptional and translational landscapes of the cell. Given that Malassezia is the most abundant fungus on human skin, we assessed the impact of the mycovirus in a murine epicutaneous infection model. Although infection with virus-infected strains was not associated with an increased inflammatory response, we did observe enhanced skin colonization in one of two virus-infected M. sympodialis strains. Noteworthy, beta interferon expression was significantly upregulated in bone marrow-derived macrophages when challenged with virus-infected, compared to virus-cured, M. sympodialis, suggesting that the presence of the virus can induce an immunological response. Although many recent studies have illuminated how widespread mycoviruses are, there are relatively few in-depth studies about their impact on disease caused by the host fungus. We describe here a novel mycovirus in Malassezia and its possible implications in pathogenicity.

Published
2020

19. Depletion of neutrophils in a protective model of pulmonary cryptococcosis results in increased IL-17A production by gamma/delta T cells

Author

Wozniak Karen L, Kolls Jay K, and Wormley Floyd L

Subjects
Gamma-delta T cells, Cryptococcus neoformans, IL-17A, Pulmonary, Immunologic diseases. Allergy, RC581-607
Abstract

Abstract Protective responses in mice immunized with an interferon-gamma producing strain of Cryptococcus neoformans, H99γ, are associated with IL-17A production by neutrophils. Neutrophil depletion in H99γ-immunized mice did not affect pulmonary fungal burden, indicating that neutrophils are not required for clearance. However, we observed an increase in IL-17A in the lungs of neutrophil-depleted H99γ infected mice, which corresponded to an increase in IL-17A+ γδ+ T cells. Moreover, we observed increased IL-17A+/ CD3+ cells and IL-17A+/γδ+ cells, but decreased IL-17A+/Ly6G+ neutrophils in the lungs of IL-17 receptor (R)A deficient mice compared to wild-type mice. Increased production of IL-17A in neutropenic mice coincided with increased IL-6 and CXCL1, but not Th17 inducing cytokines TGF-β, IL-21 and IL-23. Concurrent depletion of neutrophils and γδ+ T cells reduced IL-17A levels. Our results suggest that γδ+ T cells mediate significant IL-17A production in neutropenic mice during the protective response to C. neoformans infection.

Published
2012
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23. Th1/Th2 cytokine expression in saliva of HIV-positive and HIV-negative individuals: a pilot study in HIV-positive individuals with oropharyngeal candidiasis

Author

Leigh, Janet E., Steele, Chad, Wormley, Floyd L., Jr., Luo, Wei, Clark, Rebecca A., Gallaher, William, and Fidel, Paul L., Jr.

Subjects
Cytokines -- Physiological aspects, HIV infection -- Physiological aspects, Thrush (Mouth disease) -- Physiological aspects, Health
Abstract

The expression of Th2 cytokines in oral mucosa may predict which HIV patients might develop oral candidiasis. Th2 cytokines include interleukin-4 and interleukin-10 whereas Th1 cytokines include interleukin-2 and interferon gamma. Researchers analyzed saliva samples from 20 HIV-positive people and 25 HIV-negative people. The HIV-negative group had both Th1 and Th2 cytokines in equal proportions. The HIV-positive group had a predominance of Th2 cytokines, which seemed to be a result of a lack of Th1 cytokines. Those with oral candidiasis had an even greater excess of Th2 cytokines.

Published
1998

40. Cryptococcal Heat Shock Protein 70 Homolog Ssa1 Contributes to Pulmonary Expansion of Cryptococcus neoformans during the Afferent Phase of the Immune Response by Promoting Macrophage M2 Polarization

Author

Eastman, Alison J., primary, He, Xiumiao, additional, Qiu, Yafeng, additional, Davis, Michael J., additional, Vedula, Priya, additional, Lyons, Daniel M., additional, Park, Yoon-Dong, additional, Hardison, Sarah E., additional, Malachowski, Antoni N., additional, Osterholzer, John J., additional, Wormley, Floyd L., additional, Williamson, Peter R., additional, and Olszewski, Michal A., additional

Published
2015
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41. Repurposing auranofin as an antifungal: In vitro activity against a variety of medically important fungi.

Author

Wiederhold, Nathan P., Patterson, Thomas F., Srinivasan, Anand, Chaturvedi, Ashok K., Fothergill, Annette W., Wormley, Floyd L., Ramasubramanian, Anand K., and Lopez-Ribot, José L.

Subjects
AURANOFIN, ANTIFUNGAL agents, COMMUNICABLE disease treatment, MYCOSES, RHEUMATOID arthritis treatment, CANDIDA albicans
Abstract

Repositioning old drugs can significantly decrease the time and effort that it takes to develop novel antifungal therapeutics, which represents a pressing and unmet clinical need due to the devastating nature of fungal infections. We have previously described the activity of auranofin, a gold thiol compound used to treat rheumatoid arthritis, againstCandida albicansbiofilms. Here we evaluate its antifungal spectrum of action and describe its activity against a variety of medically important fungi. [ABSTRACT FROM PUBLISHER]

Published
2017
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