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Fungal cell wall inhibitor

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https://www.readbyqxmd.com/read/29597028/revisiting-glycoside-hydrolase-family-20-%C3%AE-n-acetyl-d-hexosaminidases-crystal-structures-physiological-substrates-and-specific-inhibitors
#1
REVIEW
Tian Liu, Yanwei Duan, Qing Yang
Glycoside hydrolase family 20 β-N-acetyl-d-hexosaminidases (GH20s) catalyze the hydrolysis of glycosidic linkages in glycans, glycoproteins and glycolipids. The diverse substrates of GH20s account for their various roles in many important bioprocesses, such as glycoprotein modification, glycoconjugate metabolism, gamete recognition and chitin degradation in fungal cell walls and arthropod exoskeletons. Defects in human GH20s cause lysosomal storage diseases, Alzheimer's disease and osteoarthritis. Similarly, lower levels of GH20s arrest arthropod molting...
March 26, 2018: Biotechnology Advances
https://www.readbyqxmd.com/read/29555787/multiplex-fluorescent-activity-based-protein-profiling-identifies-active-%C3%AE-glycosidases-and-other-hydrolases-in-plants
#2
Amjad M Husaini, Kyoko Morimoto, Balakumaran Chandrasekar, Steven Kelly, Farnusch Kaschani, Daniel Palmero, Jianbing Jiang, Markus Kaiser, Oussama Ahrazem, Hermen S Overkleeft, Renier A L van der Hoorn
With nearly 140 α-glycosidases in 14 different families, plants are well equipped with enzymes that can break the α-glucosidic bonds in a large diversity of molecules. Here, we introduce activity-based protein profiling (ABPP) of α-glycosidases in plants using α-configured cyclophellitol aziridine probes carrying various fluorophores or biotin. In Arabidopsis (Arabidopsis thaliana), these probes label members of the GH31 family of Glycosyl Hydrolases, including ER-resident α-glucosidase-II RSW3/PSL5 (Radial Swelling-3/Priority for Sweet Life-5) and Golgi-resident α-mannosidase-II HGL1, both of which trim N-glycans on glycoproteins...
March 19, 2018: Plant Physiology
https://www.readbyqxmd.com/read/29546758/bioactivity-guided-metabolite-profiling-of-feijoa-acca-sellowiana-cultivars-identifies-4-cyclopentene-1-3-dione-as-a-potent-antifungal-inhibitor-of-chitin-synthesis
#3
Mona Mokhtari, Michael D Jackson, Alistair S Brown, David F Ackerley, Nigel J Ritson, Robert A Keyzers, Andrew B Munkacsi
Pathogenic fungi continue to develop resistance against current antifungal drugs. To explore the potential of agricultural waste products as a source of novel antifungal compounds, we obtained an unbiased GC-MS profile of 151 compounds from 16 commercial and experimental cultivars of feijoa peels. Multivariate analysis correlated 93% of the compound profiles with antifungal bioactivities. Of the 18 compounds that significantly correlated with antifungal activity, 5 had not previously been described from feijoa...
March 29, 2018: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/29483123/micafungin-enhances-the-human-macrophage-response-to-candida-albicans-through-%C3%AE-glucan-exposure
#4
José Pedro Guirao-Abad, Ruth Sánchez-Fresneda, Francisco Machado, Juan Carlos Argüelles, María Martínez-Esparza
Micafungin belongs to the antifungal family of echinocandins, which act as noncompetitive inhibitors of the fungal cell wall β-1,3-d-glucan synthase. Since Candida albicans is the most prevalent pathogenic fungus in humans, we study the involvement of micafungin in the modulation of the inflammatory response developed by human tissue macrophages against C. albicans The MIC for micafungin was 0.016 μg/ml on the C. albicans SC5314 standard strain. Micafungin induced a drastic reduction in the number of exponential SC5314 viable cells, with the fungicidal effect being dependent on the cellular metabolic activity...
May 2018: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29363564/a-pectin-methylesterase-inhibitor-enhances-resistance-to-verticillium-wilt
#5
Nana Liu, Yun Sun, Yakun Pei, Xueyan Zhang, Ping Wang, Xiancai Li, Fuguang Li, Yuxia Hou
Pectins are major components of the primary plant cell wall, which functions as the primary barrier against pathogens. Pectin methylesterases (PMEs) catalyze the demethylesterification of the homogalacturonan domains of pectin in the plant cell wall. Their activity is regulated by PME inhibitors (PMEIs). Here, we provide evidence that the pectin methylesterase-inhibiting protein GhPMEI3 from cotton ( Gossypium hirsutum ) functions in plant responses to infection by the fungus Verticillium dahliae GhPMEI3 interacts with PMEs and regulates the expression of a specific fungal polygalacturonase (VdPG1)...
March 2018: Plant Physiology
https://www.readbyqxmd.com/read/29311246/candida-albicans-%C3%AE-glucan-containing-particles-increase-ho-1-expression-in-oral-keratinocytes-via-a-reactive-oxygen-species-p38-mitogen-activated-protein-kinase-nrf2-pathway
#6
Yoko Ishida, Kouji Ohta, Takako Naruse, Hiroki Kato, Akiko Fukui, Hideo Shigeishi, Hiromi Nishi, Kei Tobiume, Masaaki Takechi
Oral keratinocytes provide the first line of host defense against oral candidiasis. We speculated that interactions of fungal cell wall components with oral keratinocytes regulate the stress response against Candida infection and examined the expression of genes induced by heat-killed Candida albicans in oral immortalized keratinocytes using a cDNA microarray technique. Of 24,000 genes revealed by that analysis, we focused on HO-1, a stress-inducible gene, as its expression was increased by both heat-killed and live C...
April 2018: Infection and Immunity
https://www.readbyqxmd.com/read/29205129/dissimilar-pigment-regulation-in-serpula-lacrymans-and-paxillus-involutus-during-inter-kingdom-interactions
#7
James P Tauber, Ramses Gallegos-Monterrosa, Ákos T Kovács, Ekaterina Shelest, Dirk Hoffmeister
Production of basidiomycete atromentin-derived pigments like variegatic acid (pulvinic acid-type) and involutin (diarylcyclopentenone) from the brown-rotter Serpula lacrymans and the ectomycorrhiza-forming Paxillus involutus, respectively, is induced by complex nutrition, and in the case of S. lacrymans, bacteria. Pigmentation in S. lacrymans was stimulated by 13 different bacteria and cell-wall-damaging enzymes (lytic enzymes and proteases), but not by lysozyme or mechanical damage. The use of protease inhibitors with Bacillus subtilis or heat-killed bacteria during co-culturing with S...
January 2018: Microbiology
https://www.readbyqxmd.com/read/29193198/the-dna-methyltransferase-inhibitor-5-aza-2-deoxycytidine-affects-humicola-grisea-enzyme-activities-and-the-glucose-mediated-gene-repression
#8
João Heitor C Manfrão-Netto, Thiago M Mello-de-Sousa, Astrid R Mach-Aigner, Robert L Mach, Marcio J Poças-Fonseca
Humicola grisea var. thermoidea (Hgvt) is a thermophilic ascomycete that produces lignocellulolytic enzymes and it is proposed for the conversion of agricultural residues into useful byproducts. Drugs that inhibit the DNA methyltransferases (DNMTs) activity are employed in epigenetic studies but nothing is known about a possible effect on the production of fungal enzymes. We evaluated the effect of 5-aza-2'-deoxycytidine (5-Aza; a chemical inhibitor of DNMTs activity) on the secreted enzyme activity and on the transcription of cellulase and xylanase genes from Hgvt grown in agricultural residues and in glucose...
February 2018: Journal of Basic Microbiology
https://www.readbyqxmd.com/read/29167801/breaking-the-bad-bacillus-blocks-fungal-virulence-factors
#9
COMMENT
François L Mayer, James W Kronstad
Fungal pathogens rely on the production of specific virulence factors during infection. Inhibiting such factors generally results in reduced fungal pathogenicity. Most studies in the past have focused on understanding the molecular mechanisms of fungal virulence factor expression during mono-culture, or during interaction with the host. However, a potentially important, second type of interaction has been less well studied thus far - the interplay of fungal pathogens of humans with other microbes found in their natural habitat...
October 30, 2017: Microbial Cell
https://www.readbyqxmd.com/read/29164827/inhibitors-against-fungal-cell-wall-remodeling-enzymes
#10
Ignacio Delso, Jessika Valero-Gonzalez, Fernando Gomollón-Bel, Jorge Castro-López, Wenxia Fang, Iva Navratilova, Daan M F van Aalten, Tomás Tejero, Pedro Merino, Ramon Hurtado-Guerrero
Fungal β-1,3-glucan glucanosyltransferases are glucan-remodeling enzymes that play important roles in cell wall integrity, and are essential for the viability of pathogenic fungi and yeasts. As such, they are considered possible drug targets, although inhibitors of this class of enzymes have not yet been reported. Herein we report a multidisciplinary approach based on a structure-guided design using a highly conserved transglycosylase from Sacharomyces cerevisiae, that leads to carbohydrate derivatives with high affinity for Aspergillus fumigatus Gel4...
January 22, 2018: ChemMedChem
https://www.readbyqxmd.com/read/29112179/green-ultrasound-versus-conventional-synthesis-and-characterization-of-specific-task-pyridinium-ionic-liquid-hydrazones-tethering-fluorinated-counter-anions-novel-inhibitors-of-fungal-ergosterol-biosynthesis
#11
Nadjet Rezki, Salsabeel A Al-Sodies, Sheikh Shreaz, Rayees Ahmad Shiekh, Mouslim Messali, Vaseem Raja, Mohamed R Aouad
A series of specific task ionic liquids (ILs) based on a pyridiniumhydrazone scaffold in combination with hexafluorophosphate (PF₆(-)), tetrafluoroboron (BF₄(-)) and/or trifluoroacetate (CF₃COO(-)) counter anion, were designed and characterized by IR, NMR and mass spectrometry. The reactions were conducted under both conventional and green ultrasound procedures. The antifungal potential of the synthesized compounds 2-25 was investigated against 40 strains of Candida (four standard and 36 clinical isolates)...
November 7, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29063476/fungal-%C3%AE-glucan-activates-the-nlrp3-inflammasome-in-human-bronchial-epithelial-cells-through-ros-production
#12
Yanhua Huang, Meng Hua, Xuefan Cui
The nucleotide-binding domain and leucine-rich repeat protein 3 (NLRP3) inflammasome has developed as an important bridge between innate immune and infection recently, and has the ability to drive proteolytic procaspase-1 into bioactive caspase-1, then responsible for proteolytic processing of inflammatory cytokines IL-1β and IL-18. Fungal β-glucan, a major component of fungal cell wall, triggers inflammatory response in multiple immune cells, but rarely described in epithelial cells. Also, the relationship between fungal β-glucan and NLRP3 inflammasome is not clear yet...
February 2018: Inflammation
https://www.readbyqxmd.com/read/28981444/central-mediators-of-the-zymosan-induced-febrile-response
#13
Amanda Leite Bastos-Pereira, Daniel Fraga, Arturo Alejandro Dreifuss, Aleksander Roberto Zampronio
BACKGROUND: Zymosan is a fungal cell wall protein-carbohydrate complex that is known to activate inflammatory pathways through the Toll-like receptors and is commonly used to induce fever. Nevertheless, the central mediators that are involved in the zymosan-induced febrile response are only partially known. METHODS: The present study evaluated the participation of prostaglandins, substance P, endothelin-1 (ET-1), and endogenous opioids (eOPs) in the zymosan-induced febrile response by using inhibitors and antagonists in male Wistar rats...
November 27, 2017: Journal of Basic and Clinical Physiology and Pharmacology
https://www.readbyqxmd.com/read/28968565/long-range-molecular-dynamics-study-of-interactions-of-the-eukaryotic-glucosamine-6-phosphate-synthase-with-fructose-6-phosphate-and-udp-glcnac
#14
Aleksandra Miszkiel, Marek Wojciechowski
Glucosamine-6-phosphate synthase (EC 2.6.1.16) is responsible for catalysis of the first and practically irreversible step in hexosamine metabolism. The final product of this pathway, uridine 5' diphospho N-acetyl-d-glucosamine (UDP-GlcNAc), is an essential substrate for assembly of bacterial and fungal cell walls. Moreover, the enzyme is involved in phenomenon of hexosamine induced insulin resistance in type II diabetes, which makes of it a potential target for anti-fungal, anti-bacterial and anti-diabetic therapy...
November 2017: Journal of Molecular Graphics & Modelling
https://www.readbyqxmd.com/read/28890395/the-antifungal-arsenal-alternative-drugs-and-future-targets
#15
Nathan P Wiederhold
Clinically available antifungals for the treatment of invasive fungal infections primarily target either ergosterol in the fungal cell membrane or 1,3-β-D-glucan in the fungal cell wall. These classes include the polyene amphotericin B, the triazoles, and the echinocandins. Although newer antifungals and improved formulations of others have advanced our ability to treat patients with invasive mycoses, these drugs are often limited by toxicities, drug interactions, and the need for intravenous administration...
March 2018: International Journal of Antimicrobial Agents
https://www.readbyqxmd.com/read/28791666/clinical-pharmacokinetics-and-pharmacodynamics-of-micafungin
#16
REVIEW
Roeland E Wasmann, Eline W Muilwijk, David M Burger, Paul E Verweij, Catherijne A Knibbe, Roger J Brüggemann
Micafungin is a selective inhibitor of the synthesis of fungal 1,3-β-D-glucan, an essential component of the fungal cell wall. It is available as a powder for infusion only and is registered for the treatment of invasive and esophageal candidiasis in addition to prophylaxis of Candida infections in both adults and children. Average exposure after a single intravenous 100 mg dose in healthy adults is 133 mg h/L. Both exposure and maximum plasma concentration show linear dose proportional pharmacokinetics (PK) over a 0...
March 2018: Clinical Pharmacokinetics
https://www.readbyqxmd.com/read/28783748/heat-shock-protein-90-localizes-to-the-surface-and-augments-virulence-factors-of-cryptococcus-neoformans
#17
Sharanya Chatterjee, Utpal Tatu
BACKGROUND: Thermotolerance is an essential attribute for pathogenesis of Cryptococcus as exemplified by the fact that only two species in the genus, which can grow at 37°C, are human pathogens. Species which have other virulence factors including capsule formation and melanisation, but lack the ability to propagate at 37°C are not pathogenic. In another related fungal pathogen, Candida albicans, heat shock protein 90 has been implicated to be a central player in commanding pathogenicity by governing yeast to hyphal transition and drug resistance...
August 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28611248/the-aspergillus-fumigatus-crza-transcription-factor-activates-chitin-synthase-gene-expression-during-the-caspofungin-paradoxical-effect
#18
Laure Nicolas Annick Ries, Marina Campos Rocha, Patrícia Alves de Castro, Rafael Silva-Rocha, Roberto Nascimento Silva, Fernanda Zanolli Freitas, Leandro José de Assis, Maria Célia Bertolini, Iran Malavazi, Gustavo H Goldman
Aspergillus fumigatus is an opportunistic fungal pathogen that causes invasive aspergillosis (IA), a life-threatening disease in immunocompromised humans. The echinocandin caspofungin, adopted as a second-line therapy in combating IA, is a β-1,3-glucan synthase inhibitor, which, when used in high concentrations, reverts the anticipated A. fumigatus growth inhibition, a phenomenon called the "caspofungin paradoxical effect" (CPE). The CPE has been widely associated with increased chitin content in the cell wall due to a compensatory upregulation of chitin synthase-encoding genes...
June 13, 2017: MBio
https://www.readbyqxmd.com/read/28579986/hiv-aspartic-peptidase-inhibitors-modulate-surface-molecules-and-enzyme-activities-involved-with-physiopathological-events-in-fonsecaea-pedrosoi
#19
Vanila F Palmeira, Daniela S Alviano, Lys A Braga-Silva, Fátima R V Goulart, Marcela Q Granato, Sonia Rozental, Celuta S Alviano, André L S Santos, Lucimar F Kneipp
Fonsecaea pedrosoi is the main etiological agent of chromoblastomycosis, a recalcitrant disease that is extremely difficult to treat. Therefore, new chemotherapeutics to combat this fungal infection are urgently needed. Although aspartic peptidase inhibitors (PIs) currently used in the treatment of human immunodeficiency virus (HIV) have shown anti-F. pedrosoi activity their exact mechanisms of action have not been elucidated. In the present study, we have investigated the effects of four HIV-PIs on crucial virulence attributes expressed by F...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28469160/differential-roles-for-six-p-type-calcium-atpases-in-sustaining-intracellular-ca-2-homeostasis-asexual-cycle-and-environmental-fitness-of-beauveria-bassiana
#20
Jie Wang, Xiao-Guan Zhu, Sheng-Hua Ying, Ming-Guang Feng
A global insight into the roles of multiple P-type calcium ATPase (CA) pumps in sustaining the life of a filamentous fungal pathogen is lacking. Here we elucidated the functions of five CA pumps (Eca1, Spf1 and PmcA/B/C) following previous characterization of Pmr1 in Beauveria bassiana, a fungal insect pathogen. The fungal CA pumps interacted at transcriptional level, at which singular deletions of five CA genes depressed eca1 expression by 76-98% and deletion of spf1 resulted in drastic upregulation of four CA genes by 36-50-fold...
May 3, 2017: Scientific Reports
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