scholarly journals A chemical genetic screen reveals a role for proteostasis in capsule and biofilm formation by Cryptococcus neoformans

2018 ◽  
Vol 5 (11) ◽  
pp. 495-510 ◽  
Author(s):  
François L. Mayer ◽  
Eddy Sánchez-León ◽  
James W. Kronstad
Keyword(s):  
Cryptococcus Neoformans ◽  
Biofilm Formation ◽  
Genetic Screen ◽  
Chemical Genetic

scholarly journals Darunavir inhibits Cryptococcus neoformans/Cryptococcus gattii species complex growth and increases the susceptibility of biofilms to antifungal drugs

2020 ◽  
Vol 69 (6) ◽  
pp. 830-837
Author(s):  
Raimunda Sâmia Nogueira Brilhante ◽  
José Alexandre Telmos Silva ◽  
Géssica dos Santos Araújo ◽  
Vandbergue Santos Pereira ◽  
Wilker Jose Perez Gotay ◽  
...  
Keyword(s):  
Cryptococcus Neoformans ◽  
Amphotericin B ◽  
Metabolic Activity ◽  
Biofilm Formation ◽  
Species Complex ◽  
Cryptococcus Gattii ◽  
Antifungal Drugs ◽  
Planktonic Cells ◽  
Species Activity ◽  
Checkerboard Assay

Introduction. Cryptococcus species are pathogens commonly associated with cases of meningoencephalitis in individuals who are immunosuppressed due to AIDS. Aim. The aim was to evaluate the effects of the antiretroviral darunavir alone or associated with fluconazole, 5-flucytosine and amphotericin B against planktonic cells and biofilms of Cryptococcus species. Methodology. Susceptibility testing of darunavir and the common antifungals against 12 members of the Cryptococcus neoformans/Cryptococcus gattii species complex was evaluated by broth microdilution. The interaction between darunavir and antifungals against planktonic cells was tested by a checkerboard assay. The effects of darunavir against biofilm metabolic activity and biomass were evaluated by the XTT reduction assay and crystal violet staining, respectively. Results. Darunavir combined with amphotericin B showed a synergistic interaction against planktonic cells. No antagonistic interaction was observed between darunavir and the antifungals used. All Cryptococcus species strains were strong biofilm producers. Darunavir alone reduced biofilm metabolic activity and biomass when added during and after biofilm formation (P<0.05). The combination of darunavir with antifungals caused a significant reduction in biofilm metabolic activity and biomass when compared to darunavir alone (P<0.05). Conclusion. Darunavir presents antifungal activity against planktonic cells of Cryptococcus species and synergism with amphotericin B. In addition, darunavir led to reduced biofilm formation and showed activity against mature biofilms of Cryptococcus species. Activity of the antifungals against mature biofilms was enhanced in the presence of darunavir.

Forward chemical genetic screen for oxygen‐dependent cytotoxins uncovers new covalent fragments that target GPX4

ChemBioChem ◽  
2021 ◽  
Author(s):  
Marie Cordon ◽  
Kristian Jacobsen ◽  
Cecilie Nielsen ◽  
Per Hjerrild ◽  
Thomas Bjørnskov Poulsen
Keyword(s):  
Genetic Screen ◽  
Chemical Genetic

scholarly journals A chemical–genetic screen identifies ABHD12 as an oxidized-phosphatidylserine lipase

2019 ◽  
Vol 15 (2) ◽  
pp. 169-178 ◽  
Author(s):  
Dhanashree S. Kelkar ◽  
Govindan Ravikumar ◽  
Neelay Mehendale ◽  
Shubham Singh ◽  
Alaumy Joshi ◽  
...  
Keyword(s):  
Genetic Screen ◽  
Chemical Genetic

scholarly journals A Chemical Genetic Screen in Zebrafish for Pathways Interacting with cdx4 in Primitive Hematopoiesis

Zebrafish ◽  
2010 ◽  
Vol 7 (1) ◽  
pp. 61-68 ◽  
Author(s):  
Elizabeth J. Paik ◽  
Jill L.O. de Jong ◽  
Emily Pugach ◽  
Praise Opara ◽  
Leonard I. Zon
Keyword(s):  
Genetic Screen ◽  
Chemical Genetic ◽  
Primitive Hematopoiesis

scholarly journals Chemical Genetic Screen for AMPKα2 Substrates Uncovers a Network of Proteins Involved in Mitosis

2011 ◽  
Vol 44 (6) ◽  
pp. 878-892 ◽  
Author(s):  
Max R. Banko ◽  
Jasmina J. Allen ◽  
Bethany E. Schaffer ◽  
Erik W. Wilker ◽  
Peiling Tsou ◽  
...  
Keyword(s):  
Genetic Screen ◽  
Chemical Genetic

scholarly journals Cryptococcus neoformans Biofilm Formation Depends on Surface Support and Carbon Source and Reduces Fungal Cell Susceptibility to Heat, Cold, and UV Light

2007 ◽  
Vol 73 (14) ◽  
pp. 4592-4601 ◽  
Author(s):  
Luis R. Martinez ◽  
Arturo Casadevall
Keyword(s):  
Cryptococcus Neoformans ◽  
Biofilm Formation ◽  
Capsular Polysaccharide ◽  
Uv Light ◽  
Surface Characteristics ◽  
Extracellular Polysaccharide ◽  
Microtiter Plate ◽  
Support Surface ◽  
Fungal Cell ◽  
Biofilm Development

ABSTRACT The fungus Cryptococcus neoformans possesses a polysaccharide capsule and can form biofilms on medical devices. We describe the characteristics of C. neoformans biofilm development using a microtiter plate model, microscopic examinations, and a colorimetric 2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-5-[(phenylamino) carbonyl]-2H-tetrazolium-hydroxide (XTT) reduction assay to observe the metabolic activity of cryptococci within a biofilm. A strong correlation between XTT and CFU assays was demonstrated. Chemical analysis of the exopolymeric material revealed sugar composition consisting predominantly of xylose, mannose, and glucose, indicating the presence of other polysaccharides in addition to glucurunoxylomannan. Biofilm formation was affected by surface support differences, conditioning films on the surface, characteristics of the medium, and properties of the microbial cell. A specific antibody to the capsular polysaccharide of this fungus was used to stain the extracellular polysaccharide matrix of the fungal biofilms using light and confocal microscopy. Additionally, the susceptibility of C. neoformans biofilms and planktonic cells to environmental stress was investigated using XTT reduction and CFU assays. Biofilms were less susceptible to heat, cold, and UV light exposition than their planktonic counterparts. Our findings demonstrate that fungal biofilm formation is dependent on support surface characteristics and that growth in the biofilm state makes fungal cells less susceptible to potential environmental stresses.

scholarly journals EDTA Inhibits Biofilm Formation, Extracellular Vesicular Secretion, and Shedding of the Capsular Polysaccharide Glucuronoxylomannan by Cryptococcus neoformans

2012 ◽  
Vol 78 (22) ◽  
pp. 7977-7984 ◽  
Author(s):  
Emma J. Robertson ◽  
Julie M. Wolf ◽  
Arturo Casadevall
Keyword(s):  
Cryptococcus Neoformans ◽  
Biofilm Formation ◽  
Capsular Polysaccharide ◽  
Inhibitory Effect ◽  
Antifungal Drugs ◽  
Biofilm Growth ◽  
Content Type ◽  
Sublethal Concentrations ◽  
Vesicular Secretion

ABSTRACTThe fungal pathogenCryptococcus neoformanscan grow as a biofilm on a range of synthetic and prosthetic materials. Cryptococcal biofilm formation can complicate the placement of shunts used to relieve increased intracranial pressure in cryptococcal meningitis and can serve as a nidus for chronic infection. Biofilms are generally advantageous to pathogensin vivo, as they can confer resistance to antimicrobial compounds, including fluconazole and voriconazole in the case ofC. neoformans. EDTA can inhibit biofilm formation by several microbes and enhances the susceptibility of biofilms to antifungal drugs. In this study, we evaluated the effect of sublethal concentrations of EDTA on the growth of cryptococcal biofilms. EDTA inhibited biofilm growth byC. neoformans, and the inhibition could be reversed by the addition of magnesium or calcium, implying that the inhibitory effect was by divalent cation starvation. EDTA also reduced the amount of the capsular polysaccharide glucuronoxylomannan shed into the biofilm matrix and decreased vesicular secretion from the cell, thus providing a potential mechanism for the inhibitory effect of this cation-chelating compound. Our data imply that the growth ofC. neoformansbiofilms requires the presence of divalent metals in the growth medium and suggest that cations are required for the export of materials needed for biofilm formation, possibly including extracellular vesicles.

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