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https://www.readbyqxmd.com/read/28811501/characterisation-of-sterol-biosynthesis-and-validation-of-14%C3%AE-demethylase-as-a-drug-target-in-acanthamoeba
#1
Scott Thomson, Christopher A Rice, Tong Zhang, RuAngelie Edrada-Ebel, Fiona L Henriquez, Craig W Roberts
The soil amoebae Acanthamoeba causes Acanthamoeba keratitis, a severe sight-threatening infection of the eye and the almost universally fatal granulomatous amoebic encephalitis. More effective treatments are required. Sterol biosynthesis has been effectively targeted in numerous fungi using azole compounds that inhibit the cytochrome P450 enzyme sterol 14α-demethylase. Herein, using Gas Chromatography Mass Spectrometry (GCMS), we demonstrate that the major sterol of Acanthamoeba castellanii is ergosterol and identify novel putative precursors and intermediate sterols in its production...
August 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28811086/proteomic-profiling-of-the-antifungal-drug-response-of-aspergillus-fumigatus-to-voriconazole
#2
Nansalmaa Amarsaikhan, Daniela Albrecht-Eckardt, Christoph Sasse, Gerhard H Braus, Zumrut B Ogel, Olaf Kniemeyer
Antifungal resistance is an emerging problem and one of the reasons for treatment failure of invasive aspergillosis (IA). Voriconazole has become a standard therapeutic for the treatment of this often fatal infection. We studied the differentially expressed proteins as a response of Aspergillus fumigatus to voriconazole by employing the two-dimensional difference gel electrophoresis (DIGE) technique. Due to addition of drug, a total of 135 differentially synthesized proteins were identified by MALDI-TOF/TOF-mass spectrometry...
August 5, 2017: International Journal of Medical Microbiology: IJMM
https://www.readbyqxmd.com/read/28809155/microbe-profile-candida-albicans-a-shape-changing-opportunistic-pathogenic-fungus-of-humans
#3
Neil A R Gow, Bhawna Yadav
(a) Morphotypes of Candida albicans (blue sector, vegetative forms; pink sector, forms related to mating or changes in ploidy). Cell types shown include: budding yeast cells; elongated conjoined yeasts forming pseudohyphae; parallel-sided hyphae; chlamydospores formed from suspensor cells; enlarged goliath cells formed under zinc deprivation (unpublished study, image from Duncan Wilson); intestinal gut form cells (image from Suzanne Noble); mating competence defined by white-grey-opaque cell transitions (images from Guanghua Huang); elongated chemotactic shmoo-mating projections leading to tetraploid zygote formation (images from David Soll and Karla Daniels); trimera formed by unequal chromosome segregation under antifungal exposure (image from Judith Berman)...
August 15, 2017: Microbiology
https://www.readbyqxmd.com/read/28807921/candida-albicans-swi-snf-and-mediator-complexes-differentially-regulate-mrr1-induced-mdr1-expression-and-fluconazole-resistance
#4
Zhongle Liu, Lawrence C Myers
Long-term azole treatment of patients with chronic Candida albicans infections can lead to drug resistance. Gain-of-function (GOF) mutations in the transcription factor Mrr1 and the consequent transcriptional activation of MDR1, a drug efflux coding gene, is a common pathway by which this human fungal pathogen acquires fluconazole resistance. This work elucidates the previously unknown downstream transcription mechanisms utilized by hyperactive Mrr1. We've identified the Swi/Snf chromatin remodeling complex as a key co-activator for Mrr1, which is required to maintain basal and induced 'open' chromatin, and Mrr1 occupancy, at the MDR1 promoter...
August 14, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28807920/mediator-tail-module-is-required-for-tac1-activated-cdr1-expression-and-azole-resistance-in-candida-albicans
#5
Zhongle Liu, Lawrence C Myers
The human fungal pathogen Candida albicans develops drug resistance after long-term exposure to azole drugs in the treatment of chronic candidiasis. Gain-of-function (GOF) mutations in the transcription factor Tac1, and the consequent expression of its targets, drug efflux pumps Cdr1 and Cdr2, are a common mechanism by which C. albicans acquires fluconazole resistance. The mechanism by which GOF mutations hyperactivate Tac1 is currently unknown. Here, we define a transcriptional activation domain (TAD) at the C-terminus of Tac1...
August 14, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28802173/fungicidal-activity-of-copper-sputtered-flexible-surfaces-under-dark-and-actinic-light-against-azole-resistant-candida-albicans-and-candida-glabrata
#6
Myriam K S Ballo, Sami Rtimi, John Kiwi, César Pulgarin, José M Entenza, Alain Bizzini
Candida spp. are able to survive on hospital surfaces and causes healthcare-associated infections (HCAIs). Since surface cleaning and disinfecting interventions are not totally effective to eliminate Candida spp., new approaches should be devised. Copper (Cu) has widely recognized antifungal activity and the use of Cu-sputtered surfaces has recently been proposed to curb the spread of HCAIs. Moreover, the activity of Cu under the action of actinic light remains underexplored. We investigated the antifungal activity of Cu-sputtered polyester surfaces (Cu-PES) against azole-resistant Candida albicans and Candida glabrata under dark and low intensity visible light irradiation (4...
July 29, 2017: Journal of Photochemistry and Photobiology. B, Biology
https://www.readbyqxmd.com/read/28797882/repurposing-antipsychotic-drugs-into-antifungal-agents-synergistic-combinations-of-azoles-and-bromperidol-derivatives-in-the-treatment-of-various-fungal-infections
#7
Selina Y L Holbrook, Atefeh Garzan, Emily K Dennis, Sanjib K Shrestha, Sylvie Garneau-Tsodikova
As the number of hospitalized and immunocompromised patients continues to rise, invasive fungal infections, such as invasive candidiasis and aspergillosis, threaten the life of millions of patients every year. The azole antifungals are currently the most prescribed drugs clinically that display broad-spectrum antifungal activity and excellent oral bioavailability. Yet, the azole antifungals have their own limitations and are unable to meet the challenges associated with increasing fungal infections and the accompanied development of resistance against azoles...
July 19, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28797486/diagnosis-and-management-of-coccidioidomycosis
#8
REVIEW
Luke M Gabe, Joshua Malo, Kenneth S Knox
Coccidioidomycosis is a leading cause of community-acquired pneumonia within its traditional endemic zone in the Southwestern United States and portions of Mexico and Central and South America. Its incidence has increased dramatically within the endemic region; its presence outside of the region, facilitated by a mobile society, is also now substantial. Although only a fraction of the incident disease progresses beyond subclinical illness, this proportion is large in absolute terms and causes substantial disease burden...
September 2017: Clinics in Chest Medicine
https://www.readbyqxmd.com/read/28797484/overview-of-treatment-approaches-for-fungal-infections
#9
REVIEW
Eva M Carmona, Andrew H Limper
Invasive fungal diseases cause high morbidity and mortality in an immunocompromised host. Antifungals are the drugs of choice and can be divided into 4 main groups: polyenes, azoles, echinocandins, and pyrimidine analogues. Each class has its specific mechanism of action, spectrum of activity, and pharmacokinetic and side effects. It is important to understand the precise use of the established and new antifungal agents to successfully manage these complex infections in an already tenuous and frail host. This article discusses the main characteristics, clinical uses, and secondary effects of the main antifungals used in clinical practice...
September 2017: Clinics in Chest Medicine
https://www.readbyqxmd.com/read/28795522/assessment-of-carvacrol-for-control-of-avian-aspergillosis-in-intratracheally-challenged-chickens-in-comparison-to-voriconazole-with-a-reference-on-economic-impact
#10
Y H Tartor, F A M Hassan
AIM: This study was designed to investigate the efficacy of essential oils (EOs) as an alternative prophylaxis and treatment for avian aspergillosis. METHODS AND RESULTS: The in vitro susceptibility of A. fumigatus strains to antifungal drugs and carvacrol, thymol, eugenol, thymoquinone and cinnamon was determined using the macro-diffusion and microdilution methods. Carvacrol has antifungal activity in comparison to voriconazole (VCZ) (MIC 0.5, 0.25μg/ml, respectively)...
August 9, 2017: Journal of Applied Microbiology
https://www.readbyqxmd.com/read/28795298/pharmacokinetics-of-azole-antifungals-in-cystic-fibrosis
#11
REVIEW
Ryan M Rivosecchi, Palash Samanta, Moses Demehin, M Hong Nguyen
Defects in mucociliary clearance predispose cystic fibrosis (CF) patients to airway colonization and infection by various fungi, especially Aspergillus fumigatus. Although the clinical significance of airway fungal colonization is not clear, several studies have suggested its association with worsening lung function and increased risk of CF exacerbations. Antifungal triazole agents have been used in CF patients with airway fungal colonization or infections with varying results. Limited pharmacokinetic studies to date have demonstrated high inter-subject variability of triazole levels among CF patients...
August 9, 2017: Mycopathologia
https://www.readbyqxmd.com/read/28793202/differential-inhibition-of-rat-and-mouse-microsome-heme-oxygenase-by-derivatives-of-imidazole-and-benzimidazole
#12
Maaike Hum, Brian E McLaughlin, Xianqi Kong, Jason Z Vlahakis, Dragic Vukomanovic, Walter A Szarek, Kanji Nakatsu
Metalloporphyrin, heme oxygenase (HO) inhibitors have made an important contribution to elucidating the role of HO in physiological processes. Nevertheless, their off-target effects have drawn substantial criticism, which prompted us to develop non-porphyrin, azole-based inhibitors of HO. These second-generation HO inhibitors were evaluated using spleen and brain microsomes from rats as native sources of HO-1 and HO-2, respectively. Recently, the use of azole-based inhibitors of HO has been extended to other mammalian species and, as a consequence, it will be important to characterize the inhibitors in these species...
August 9, 2017: Canadian Journal of Physiology and Pharmacology
https://www.readbyqxmd.com/read/28793019/cryptococcus-neoformans-and-c-gattii-isolates-from-both-hiv-infected-and-uninfected-patients-antifungal-susceptibility-and-outcome-of-cryptococcal-disease
#13
Erika Nascimento, Lucia Helena Vitali, Marcia Regina von Zeska Kress, Roberto Martinez
One of the factors causing treatment failure in cryptococcosis is the resistance of Cryptococcus spp. to antifungal drugs, which has motivated the susceptibility assessment of isolates from patients with cryptococcosis, different clinical conditions and infections outcomes. Clinical isolates of Cryptococcus spp. from three different groups of patients were studied in the present investigation: 19 HIV-positive patients with relapsing and/or refractory meningitis (Group 1), 30 HIV-positive patients who experienced a single and limited episode of cryptococcosis (Group 2), and 19 HIV-negative patients with cryptococcosis (Group 3)...
2017: Revista do Instituto de Medicina Tropical de São Paulo
https://www.readbyqxmd.com/read/28776447/analysis-of-imidazoles-and-triazoles-in-biological-samples-after-microextraction-by-packed-sorbent
#14
Cristina Campestre, Marcello Locatelli, Paolo Guglielmi, Elisa De Luca, Giuseppe Bellagamba, Sergio Menta, Gokhan Zengin, Christian Celia, Luisa Di Marzio, Simone Carradori
This paper reports the MEPS-HPLC-DAD method for the simultaneous determination of 12 azole drugs (bifonazole, butoconazole, clotrimazole, econazole, itraconazole, ketoconazole, miconazole, posaconazole, ravuconazole, terconazole, tioconazole and voriconazole) administered to treat different systemic and topical fungal infections, in biological samples. Azole drugs separation was performed in 36 min. The analytical method was validated in the ranges as follows: 0.02-5 μg mL(-1) for ravuconazole; 0.2-5 μg mL(-1) for terconazole; 0...
December 2017: Journal of Enzyme Inhibition and Medicinal Chemistry
https://www.readbyqxmd.com/read/28774699/pulmonary-and-sinus-fungal-diseases-in-non-immunocompromised-patients
#15
REVIEW
David W Denning, Arunaloke Chakrabarti
The human respiratory tract is exposed daily to airborne fungi, fungal enzymes, and secondary metabolites. The endemic fungi Histoplasma capsulatum, Coccidioides spp, Blastomyces dermatitidis, and Paracoccidioides brasiliensis, and occasionally Aspergillus fumigatus, are primary pulmonary pathogens of otherwise healthy people. Such infections resolve in most people, and only a few infections lead to disease. However, many fungi are directly allergenic by colonising the respiratory tract or indirectly through contact with cell wall constituents and proteases, causing or exacerbating allergic disease...
July 31, 2017: Lancet Infectious Diseases
https://www.readbyqxmd.com/read/28774698/the-global-problem-of-antifungal-resistance-prevalence-mechanisms-and-management
#16
REVIEW
David S Perlin, Riina Rautemaa-Richardson, Ana Alastruey-Izquierdo
All serious fungal infections need appropriate antifungal therapy for successful patient outcome. Only a few classes of antifungal drugs are available, so the emergence of resistance to single drug classes and now multidrug resistance greatly hampers patient management. Azole resistance among Candida and Aspergillus species is one of the greatest challenges to clinical success, followed by echinocandin and multidrug resistance among some Candida species, especially Candida glabrata. The spread of agriculturally derived azole-resistant Aspergillus fumigatus and emerging threats such as multidrug resistant Candida auris are also alarming...
July 31, 2017: Lancet Infectious Diseases
https://www.readbyqxmd.com/read/28756713/coumarinderivatives-an-updated-patent-review-2015-2016
#17
Anastasia Detsi, Christos Kontogiorgis, Dimitra Hadjipavlou-Litina
INTRODUCTION: Coumarins belong to the benzopyrone family. They are naturally plant-derived or synthetically obtained substances, presenting a wide variety of biological activities, offering an extented therapeutic profile. Their structural characteristics correlated to physicochemical properties define their pleiotropic biological responses. AREAS COVERED IN THIS REVIEW: Recent patent publications (2015-2016), describing coumarins and their derivatives are analyzed...
July 31, 2017: Expert Opinion on Therapeutic Patents
https://www.readbyqxmd.com/read/28756598/risk-factors-and-predictors-of-mortality-of-candidaemia-among-critically-ill-patients-role-of-antifungal-prophylaxis-in-its-development-and-in-selection-of-non-albicans-species
#18
Matthaios Papadimitriou-Olivgeris, Anastasia Spiliopoulou, Fotini Fligou, Iris Spiliopoulou, Lora Tanaseskou, Georgios Karpetas, Markos Marangos, Evangelos D Anastassiou, Myrto Christofidou
PURPOSE: The aim of the present study is to identify risk factors for development and predictors of mortality of candidaemia among critically ill patients. METHODS: A 1:7 case-control study was conducted during a 4-year period (2012-2015) in a Greek Intensive Care Unit (ICU). Candidaemia was confirmed by positive blood cultures. All yeasts were identified using API 20C AUX System or Vitek 2 Advanced Expert System. Epidemiologic data were collected from the ICU computerized database and patients' chart reviews...
July 29, 2017: Infection
https://www.readbyqxmd.com/read/28754462/in-vitro-susceptibility-of-candida%C3%A2-albicans-clinical-isolates-to-eight-antifungal-agents-in-ouagadougou-burkina-faso
#19
A Zida, A Yacouba, S Bamba, I Sangare, M Sawadogo, T Guiguemde, S Kone, L K Traore, R Ouedraogo-Traore, R T Guiguemde
INTRODUCTION: In recent years, the infection Candida albicans infection worldwide has risen, and the incidence of resistance to traditional antifungal therapies is also increasing. The aim of this study was to evaluate in vitro susceptibility of C. albicans clinical isolates to eight antifungal agents in Ouagadougou. MATERIALS AND METHODS: A cross-sectional study was conducted from January 2013 to December 2015 at Yalgado Ouédraogo University Teaching Hospital...
July 25, 2017: Journal de Mycologie Médicale
https://www.readbyqxmd.com/read/28751884/accumulation-of-azole-drugs-in-the-fungal-plant-pathogen-magnaporthe-oryzae-is-the-result-of-facilitated-diffusion-influx
#20
Brooke D Esquivel, Theodore C White
Magnaporthe oryzae is an agricultural mold that causes disease in rice, resulting in devastating crop losses. Since rice is a world-wide staple food crop, infection by M. oryzae poses a serious global food security threat. Fungicides, including azole antifungals, are used to prevent and combat M. oryzae plant infections. The target of azoles is CYP51, an enzyme localized on the endoplasmic reticulum (ER) and required for fungal ergosterol biosynthesis. However, many basic drug-pathogen interactions, such as how the azole gets past the fungal cell wall and plasma membrane, and is transported to the ER, are not understood...
2017: Frontiers in Microbiology
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