scholarly journals Tetracycline alters drug susceptibility in Candida albicans and other pathogenic fungi

Microbiology ◽  
2008 ◽  
Vol 154 (3) ◽  
pp. 960-970 ◽  
Author(s):  
Brian G. Oliver ◽  
Peter M. Silver ◽  
Chelsea Marie ◽  
Samantha J. Hoot ◽  
Sarah E. Leyde ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Pathogenic Fungi ◽  
Drug Susceptibility

scholarly journals A novel Hsp90 phospho-switch modulates virulence in the major human fungal pathogen Candida albicans

2020 ◽  
Author(s):  
Leenah Alaalm ◽  
Julia L. Crunden ◽  
Mark Butcher ◽  
Ulrike Obst ◽  
Ryann Whealy ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Stress Responses ◽  
Fungal Pathogen ◽  
Drug Targets ◽  
Fungal Infections ◽  
Pathogenic Fungi ◽  
First Record ◽  
Drug Susceptibility ◽  
Phosphorylation Sites ◽  
Fungal Virulence

The ubiquitous molecular chaperone Hsp90 is a key regulator of cellular proteostasis and environmental stress responses. Hsp90 also regulates cellular morphogenesis, drug resistance, and virulence in human pathogenic fungi, which kill more than 1.6 million patients each year worldwide. Invasive fungal infections are difficult to treat due to the lack of effective antifungal therapies, resulting in mortality rates of up to 95%. As a key regulator of fungal virulence, Hsp90 is an attractive therapeutic target. However, fungal and animal homologs are highly conserved, impeding fungal-specific targeting. Thus, understanding the factors that regulate Hsp90 could provide an alternative strategy aimed at exclusively targeting this regulator of fungal virulence. Here, we demonstrate how CK2-mediated phosphorylation of two Hsp90 residues modulates virulence in a major fungal pathogen of humans, Candida albicans. We combined proteomics, molecular evolution and structural modelling with molecular biology to identify and characterize two Hsp90 phosphorylation sites. Phosphorylation negatively affects thermal stress response, morphogenesis, drug susceptibility and fungal virulence. Our results provide the first record of specific Hsp90 phosphorylation sites acting as modulators of fungal virulence. Post-translational modifications of Hsp90 could prove valuable in future exploitation as antifungal drug targets.

scholarly journals In Fungal Intracellular Pathogenesis, Form Determines Fate

mBio ◽  
2018 ◽  
Vol 9 (5) ◽  
Author(s):  
Robin C. May ◽  
Arturo Casadevall
Keyword(s):  
Candida Albicans ◽  
Fungal Pathogen ◽  
Membrane Integrity ◽  
Pathogenic Fungi ◽  
Morphological Transition ◽  
Physical Damage ◽  
Fungal Cell ◽  
Morphological Transitions ◽  
Pathogenic Microbes ◽  
Phagosomal Membrane

ABSTRACT For pathogenic microbes to survive ingestion by macrophages, they must subvert powerful microbicidal mechanisms within the phagolysosome. After ingestion, Candida albicans undergoes a morphological transition producing hyphae, while the surrounding phagosome exhibits a loss of phagosomal acidity. However, how these two events are related has remained enigmatic. Now Westman et al. (mBio 9:e01226-18, 2018, https://doi.org/10.1128/mBio.01226-18) report that phagosomal neutralization results from disruption of phagosomal membrane integrity by the enlarging hyphae, directly implicating the morphological transition in physical damage that promotes intracellular survival. The C. albicans intracellular strategy shows parallels with another fungal pathogen, Cryptococcus neoformans, where a morphological changed involving capsular enlargement intracellularly is associated with loss of membrane integrity and death of the host cell. These similarities among distantly related pathogenic fungi suggest that morphological transitions that are common in fungi directly affect the outcome of the fungal cell-macrophage interaction. For this class of organisms, form determines fate in the intracellular environment.

The Multiple Chitin Synthase Genes of Candida Albicans and Other Pathogenic Fungi — A Review

1993 ◽  
pp. 51-59 ◽  
Author(s):  
P. W. Robbins ◽  
A. R. Bowen ◽  
J. L. Chen-Wu ◽  
M. Momany ◽  
P. J. Szaniszlo ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Pathogenic Fungi ◽  
Chitin Synthase

scholarly journals Potentially pathogenic fungi in the material collected by the Specialist Regional Hospital, Łódź

2013 ◽  
Vol 45 (2) ◽  
pp. 197-205
Author(s):  
Magdalena Rusicka ◽  
Grażyna Lipowczan
Keyword(s):  
Candida Albicans ◽  
Trichophyton Rubrum ◽  
Pathogenic Fungi ◽  
Regional Hospital ◽  
Pathological Changes ◽  
Superficial Mycosis

The mycobiota responsible for the development of pathological changes of the skin and its adnexa in patients presenting at the Specialist Regional Hospital, Łódź, with suspected superficial mycosis between 01 May 2003 and 30 April 2005 is analyzed. In total of 2144 isolations 39.96% were dermatophytes, 39.39% were yeast-like fungi and 20.65% were moulds. <em>Candida albicans</em> was the most frequently diagnosed species in fallowed by <em>Trichophyton rubrum</em>.

scholarly journals ANTI-CANDIDA ALBICANS ACTIVITY OF THE ASSOCIATION OF CITRONELAL WITH ANFOTERICIN B OR WITH CETOCONAZOLE

2019 ◽  
Vol 16 (31) ◽  
pp. 250-257
Author(s):  
Patrícia Duarte Costa SILVA ◽  
Brenda Lavínia Calixto dos SANTOS ◽  
Gustavo Lima SOARES ◽  
Wylly Araújo de OLIVEIRA
Keyword(s):  
Candida Albicans ◽  
Antifungal Activity ◽  
Amphotericin B ◽  
Inhibitory Concentration ◽  
Fungal Infections ◽  
Pathogenic Fungi ◽  
Mortality Rates ◽  
New Drugs ◽  
High Morbidity ◽  
Isolated Species

Fungal infections caused by species of the genus Candida are responsible for high morbidity and mortality rates, mainly affecting immunocompromised individuals. Among fungi, Candida albicans is the most frequently isolated species of clinical specimens. A problem associated with increased resistance of pathogenic fungi to the agents used in the therapeutic regimen and the limited number of drugs to cure these infections. As a result, the search for new drugs with antifungal activity has become increasingly important. The aim of this study is to study the antifungal activity of citronellal alone and in combination with amphotericin B or ketoconazole. The Minimal Inhibitory Concentration of citronellal, amphotericin B and ketoconazole against strains of Candida albicans were evaluated by the microdilution technique, and the Minimum Fungicide Concentration of citronellal against the same strains was also performed. Through the checkerboard methodology the effect of the combination of citronelal with amphotericin B or with ketoconazole was determined. This study showed that the association of citronellal with ketoconazole was shown to be an additive against one of the strains of C. albicans and indifferent to another strain. While the combined activity of citronellal and amphotericin B demonstrated an indifferent effect on the strains tested.

scholarly journals PERBANDINGAN KEMAMPUAN EKSTRAK KULIT PISANG AGUNG SEMERU DAN PISANG MAS KIRANA VARIETAS LUMAJANG DALAM MENGHAMBAT PERTUMBUHAN Candida albicans

2017 ◽  
Vol 4 (2) ◽  
pp. 31
Author(s):  
Dwi Nur Rikhmasari
Keyword(s):  
Candida Albicans ◽  
Antifungal Activity ◽  
Pathogenic Fungi ◽  
Optimal Concentration ◽  
Banana Peel ◽  
Anova Test ◽  
Random Design ◽  
The Difference ◽  
Peel Extract ◽  
Better Than

<p align="center"> </p><p><em>A</em><em>gung Semeru </em><em>banana </em><em>and </em><em>M</em><em>as Kirana, is one of the typical banana varieties found in Lumajang Regency. Where on the </em><em>banana peel extraction</em><em> contain various antifungi compounds. The purpose of this research is to know the difference of banana extract of Agung Semeru and banana Mas Kirana varieties of lumajang, in inhibiting the growth of pathogenic fungi Candida albicans, and to know the optimal concentration which can inhibit the growth of Candida albicans. The method used was Completely Random Design (RAL) with four of factors, that is: 0, 25, 50, 75 and 100 %. The results were analyzed with Anova test and Duncan test multiple ranger test at the level of 5%. Each treatment was repeated three times. </em><em>The results show that there is an effect of giving extract of Semeru banana peel (sig = 0,00) and banana Mas Kirana (sig = 0,00) to Candida albicans growth at various concentration (0%, 25%, 50%, 75% and 100%). For extract of Semeru banana peel at concentration 75% (</em><em>3,19  ± 0,84</em><em> mm) showed better result from other concentration, while for banana Mas Kirana Lumajang peel extract, at concentration 50% (</em><em>2,44 ± 0,0 mm</em><em>) showed better result than treatment other. Ability of antifungal activity of Agung Semeru banana peel extract better than banana Mas Kirana.</em></p><p><em> </em></p>

scholarly journals Synergistic Effect of Calcineurin Inhibitors and Fluconazole against Candida albicans Biofilms

2008 ◽  
Vol 52 (3) ◽  
pp. 1127-1132 ◽  
Author(s):  
Priya Uppuluri ◽  
Jeniel Nett ◽  
Joseph Heitman ◽  
David Andes
Keyword(s):  
Candida Albicans ◽  
Calcineurin Inhibitors ◽  
Drug Susceptibility ◽  
Specific Protein ◽  
Therapeutic Interventions ◽  
Ergosterol Biosynthesis ◽  
Drug Synergism ◽  
Planktonic Cells

ABSTRACT Calcineurin is a Ca2+-calmodulin-activated serine/threonine-specific protein phosphatase that governs multiple aspects of fungal physiology, including cation homeostasis, morphogenesis, antifungal drug susceptibility, and virulence. Growth of Candida albicans planktonic cells is sensitive to the calcineurin inhibitors FK506 and cyclosporine A (CsA) in combination with the azole antifungal fluconazole. This drug synergism is attributable to two effects: first, calcineurin inhibitors render fluconazole fungicidal rather than simply fungistatic, and second, membrane perturbation by azole inhibition of ergosterol biosynthesis increases intracellular calcineurin inhibitor concentrations. C. albicans cells in biofilms are up to 1,000-fold more resistant to fluconazole than planktonic cells. In both in vitro experiments and in an in vivo rat catheter model, C. albicans cells in biofilms were resistant to individually delivered fluconazole or calcineurin inhibitors but exquisitely sensitive to the combination of FK506-fluconazole or CsA-fluconazole. C. albicans strains lacking FKBP12 or expressing a dominant FK506-resistant calcineurin mutant subunit (Cnb1-1) formed biofilms that were resistant to FK506-fluconazole but susceptible to CsA-fluconazole, demonstrating that drug synergism is mediated via direct calcineurin inhibition. These findings reveal that calcineurin contributes to fluconazole resistance of biofilms and provide evidence that synergistic drug combinations may prove efficacious as novel therapeutic interventions to treat or prevent biofilms.

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