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Candida drug resistance

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https://www.readbyqxmd.com/read/28634471/a-chitin-binding-protein-purified-from-moringa-oleifera-seeds-presents-anticandidal-activity-by-increasing-cell-membrane-permeability-and-reactive-oxygen-species-production
#1
João X S Neto, Mirella L Pereira, Jose T A Oliveira, Lady C B Rocha-Bezerra, Tiago D P Lopes, Helen P S Costa, Daniele O B Sousa, Bruno A M Rocha, Thalles B Grangeiro, José E C Freire, Ana Cristina O Monteiro-Moreira, Marina D P Lobo, Raimunda S N Brilhante, Ilka M Vasconcelos
Candida species are opportunistic pathogens that infect immunocompromised and/or immunosuppressed patients, particularly in hospital facilities, that besides representing a significant threat to health increase the risk of mortality. Apart from echinocandins and triazoles, which are well tolerated, most of the antifungal drugs used for candidiasis treatment can cause side effects and lead to the development of resistant strains. A promising alternative to the conventional treatments is the use of plant proteins...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28630940/fluconazole-induced-ploidy-change-in-cryptococcus-neoformans-results-from-the-uncoupling-of-cell-growth-and-nuclear-division
#2
Sophie Altamirano, Diana Fang, Charles Simmons, Shreyas Sridhar, Peipei Wu, Kaustuv Sanyal, Lukasz Kozubowski
Cryptococcus neoformans is a pathogenic yeast that causes lethal cryptococcal meningitis in immunocompromised patients. One of the challenges in treating cryptococcosis is the development of resistance to azole antifungals. Previous studies linked azole resistance to elevated numbers of copies of critical resistance genes in aneuploid cells. However, how aneuploidy is formed in the presence of azole drugs remains unclear. This study showed that treatment with inhibitory concentrations of an azole drug, fluconazole (FLC), resulted in a significant population of cells with increased DNA content, through the following defects: inhibition of budding, premature mitosis, and inhibition of cytokinesis followed by replication in the mother cell...
May 2017: MSphere
https://www.readbyqxmd.com/read/28630180/de-novo-acquisition-of-resistance-to-scy-078-in-candida-glabrata-involves-fks-mutations-that-both-overlap-and-are-distinct-from-those-conferring-echinocandin-resistance
#3
Cristina Jiménez-Ortigosa, Winder B Perez, David Angulo, Katyna Borroto-Esoda, David S Perlin
SCY-078 is an orally active antifungal whose target is the β-(1,3)-D-glucan synthase (GS). We evaluated the spontaneous emergence of SCY-078 resistant Candida glabrata isolates following drug exposure in vitro Resistant isolates were analyzed using broth microdilution methodology and FKS sequencing. The kinetic inhibition parameter IC50 was also determined from GS complexes. The spectrum of resistance mutations found suggested a partially overlapping but independent binding site for SCY-078 relative to echinocandins on GS...
June 19, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28629056/antimicrobial-and-antioxidant-potentials-of-biosynthesized-colloidal-zinc-oxide-nanoparticles-for-a-fortified-cold-cream-formulation-a-potent-nanocosmeceutical-application
#4
Sonia S, Linda Jeeva Kumari H, Ruckmani K, Sivakumar M
Nanocosmeceuticals are promising applications of nanotechnology in personal care industries. Zinc oxide is an inorganic material that is non-toxic and skin compatible with self-cleansing and microbicidal properties. Herein, exploitation of colloidal zinc oxide nanoparticles (ZnONps) as potent biomaterial for a topical formulation of cosmetic and dermatological significance is employed. ZnONps were green synthesized using environmentally benign Adhatoda vasica leaf extract and characterized by UV-Vis absorption spectroscopy, Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), dynamic light scattering (DLS), high-resolution transmission electron microscopy (HR-TEM) and energy-dispersive X-ray spectroscopy (EDX)...
October 1, 2017: Materials Science & Engineering. C, Materials for Biological Applications
https://www.readbyqxmd.com/read/28617137/drugs-currently-under-investigation-for-the-treatment-of-invasive-candidiasis
#5
Matthew W McCarthy, Thomas J Walsh
The widespread implementation of immunosuppressants, immunomodulators, hematopoietic stem cell transplantation and solid organ transplantation in clinical practice has led to an expanding population of patients who are at risk for invasive candidiasis, which is the most common form of fungal disease among hospitalized patients in the developed world. The emergence of drug-resistant Candida spp. has added to the morbidity associated with invasive candidiasis and novel therapeutic strategies are urgently needed...
June 15, 2017: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/28611662/an-antifungal-mechanism-of-protolichesterinic-acid-from-the-lichen-usnea-albopunctata-lies-in-the-accumulation-of-intracellular-ros-and-mitochondria-mediated-cell-death-due-to-apoptosis-in-candida-tropicalis
#6
S N Kumar, C Mohandas
Candida species causes superficial and life-threatening systemic infections and are difficult to treat due to the resistance of these organism to various clinically used drugs. Protolichesterinic acid is a well-known lichen compound. Although the antibacterial activity of protolichesterinic acid has been reported earlier, the antifungal property and its mechanism of action are still largely unidentified. The goal of the present investigation is to explore the anticandidal activity and mechanism of action of protolichesterinic acid, especially against Candida tropicalis...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28610983/design-and-synthesis-of-a-novel-inhibitor-of-t-viride-chitinase-through-an-in-silico-target-fishing-protocol
#7
Giorgio Maccari, Davide Deodato, Diego Fiorucci, Francesco Orofino, Giuseppina I Truglio, Carolina Pasero, Riccardo Martini, Filomena De Luca, Jean-Denis Docquier, Maurizio Botta
In the last ten years, we identified and developed a new therapeutic class of antifungal agents, the macrocyclic amidinoureas. These compounds are active against several Candida species, including clinical isolates resistant to currently available antifungal drugs. The mode of action of these molecules is still unknown. In this work, we developed an in-silico target fishing procedure to identify a possible target for this class of compounds based on shape similarity, inverse docking procedure and consensus score rank-by-rank...
June 10, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28605112/candida-albicans-biofilms-comparative-analysis-of-room-temperature-and-cryofixation-for-scanning-electron-microscopy
#8
T Vila, B B Fonseca, M M L DA Cunha, G R C Dos Santos, K Ishida, E Barreto-Bergter, W DE Souza, S Rozental
Biofilms are frequently related to invasive fungal infections and are reported to be more resistant to antifungal drugs than planktonic cells. The structural complexity of the biofilm as well as the presence of a polymeric extracellular matrix (ECM) is thought to be associated with this resistant behavior. Scanning electron microscopy (SEM) after room temperature glutaraldehyde-based fixation, have been used to study fungal biofilm structure and drug susceptibility but they usually fail to preserve the ECM and, therefore, are not an optimised methodology to understand the complexity of the fungal biofilm...
June 12, 2017: Journal of Microscopy
https://www.readbyqxmd.com/read/28588560/molecular-epidemiology-and-antifungal-susceptibility-of-candida-glabrata-in-china-august-2009-to-july-2014-a-multi-center-study
#9
Xin Hou, Meng Xiao, Sharon C-A Chen, Fanrong Kong, He Wang, Yun-Zhuo Chu, Mei Kang, Zi-Yong Sun, Zhi-Dong Hu, Ruo-Yu Li, Juan Lu, Kang Liao, Tie-Shi Hu, Yu-Xing Ni, Gui-Ling Zou, Ge Zhang, Xin Fan, Yu-Pei Zhao, Ying-Chun Xu
Candida glabrata is an increasingly important cause of invasive candidiasis. In China, relatively little is known of the molecular epidemiology of C. glabrata and of its antifungal susceptibility patterns. Here we studied 411 non-duplicate C. glabrata isolates from 411 patients at 11 hospitals participating in the National China Hospital Invasive Fungal Surveillance Net program (CHIF-NET; 2010-2014). Genotyping was performed using multilocus sequence typing (MLST) employing six genetic loci and by microsatellite analysis...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28587870/evaluation-of-the-in-vitro-antimicrobial-activity-of-selected-saudi-scorpion-venoms-tested-against-multidrug-resistant-micro-organisms
#10
Abdulrahman K Al-Asmari, Meshref Ali Alamri, Aqeel Salman Almasoudi, Rajamohamed Abbasmanthiri, Maysa Mahfoud
OBJECTIVES: Scorpion venoms are a rich source of bioactive peptides with promising clinical value that may lead to the discovery and development of new drugs. The present study was designed to evaluate the in vitro antimicrobial activities of the venoms extracted from three medically important Saudi scorpions (Androctonus crassicauda, Androctonus bicolor and Leiurus quinquestriatus). METHODS: Antimicrobial assays were performed using a microplate growth inhibition assay against 10 multidrug-resistant (MDR) micro-organisms (4 Gram-negative bacteria, 2 Gram-positive bacteria and 4 fungi and yeasts) at concentrations ranging from 0 to 20mg/mL of each venom...
June 3, 2017: Journal of Global Antimicrobial Resistance
https://www.readbyqxmd.com/read/28584446/antimicrobial-activity-of-various-ethanolic-plant-extracts-against-pathogenic-multi-drug-resistant-candida-spp
#11
Shaista Khan, Mohd Imran, Mohammed Imran, Nuzhat Pindari
A total of 50 Candida isolates were isolated and identified from clinical specimens and these were tested for resistance to various antifungal drugs. It was observed multi-drug resistance in all candida isolates by 84%, 62%, 60%, 76%, 46, 30%, and 22% against fluconazole, clotrimazole, Amphotericin B, itraconazole, ketoconazole, miconazole and nystatin tested respectively. The isolates, which were found to be resistant to antifungal drugs were selected and subjected to antifungal testing against six ethanolic plants, extract namely Azadiracta indica, Allium sativum, Cordia dichotoma Ocimum sanctum, Syzygium cumini and Trigonella foenum grecum...
2017: Bioinformation
https://www.readbyqxmd.com/read/28584152/pharmacodynamic-optimization-for-treatment-of-invasive-candida-auris-infection
#12
Alexander J Lepak, Miao Zhao, Elizabeth L Berkow, Shawn R Lockhart, David R Andes
Candida auris is an emerging, multidrug-resistant threat. The pharmacodynamics of three antifungal classes against nine C. auris strains was explored using a murine invasive candidiasis model. The total drug median PD target associated with net stasis was a fluconazole AUC/MIC of 26, amphotericin B Cmax/MIC of 0.9, and micafungin AUC/MIC of 54. The micafungin PD targets for C. auris were ≥20-fold lower than other Candida species in this animal model. Clinically relevant micafungin exposures produced the most killing among the three classes...
June 5, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28566663/promising-therapies-for-fungal-infection-based-on-the-study-to-elucidate-mechanisms-to-cope-with-stress-in-candida-species-translated-article
#13
Kazuyuki Hirai, Tatsuya Inukai, Hironobu Nakayama
In recent years, the incidence of fungal infections has been increasing, particularly among patients with immune systems compromised by human immunodeficiency virus infection, organ transplantation, and/or chemotherapy for cancer. Current therapies for treating systemic fungal infection have limited effectiveness and have created problems of adverse reactions and drug resistance. These issues therefore motivate us to develop novel antifungals. Elucidation of stress response mechanisms and virulence factors in pathogenic fungi is required in developing an effective antifungal strategy...
2017: Medical Mycology Journal
https://www.readbyqxmd.com/read/28559486/mismatch-repair-of-dna-replication-errors-contributes-to-microevolution-in-the-pathogenic-fungus-cryptococcus-neoformans
#14
Kylie J Boyce, Yina Wang, Surbhi Verma, Viplendra P S Shakya, Chaoyang Xue, Alexander Idnurm
The ability to adapt to a changing environment provides a selective advantage to microorganisms. In the case of many pathogens, a large change in their environment occurs when they move from a natural setting to a setting within a human host and then during the course of disease development to various locations within that host. Two clinical isolates of the human fungal pathogen Cryptococcus neoformans were identified from a collection of environmental and clinical strains that exhibited a mutator phenotype, which is a phenotype which provides the ability to change rapidly due to the accumulation of DNA mutations at high frequency...
May 30, 2017: MBio
https://www.readbyqxmd.com/read/28559186/multidrug-abc-transporter-cdr1-of-candida-albicans-harbors-specific-and-overlapping-binding-sites-for-human-steroid-hormones-transport
#15
Pratima Baghel, Manpreet Kaur Rawal, Mohammad Firoz Khan, Sobhan Sen, Mohammed Haris Siddiqui, Vincent Chaptal, Pierre Falson, Rajendra Prasad
The present study examines the kinetics of steroids efflux mediated by the Candida drug resistance protein 1 (Cdr1p) and evaluates their interaction with the protein. We exploited our in-house mutant library for targeting the 252 residues forming the twelve transmembrane helices (TMHs) of Cdr1p. The screening revealed 65 and 58 residues critical for β-estradiol and corticosterone transport, respectively. Notably, up to 83% critical residues for corticosterone face the lipid interface compared to 54% for β-estradiol...
May 27, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28558440/chemical-composition-and-antimicrobial-activities-of-iranian-propolis
#16
Houshang Afrouzan, Tahghighi Azar, Sedigheh Zakeri, Es-haghi Ali
Background: With considering the importance of natural products for their remedial and therapeutic value, this research was aimed to analyze the chemical compositions and antimicrobial activity of four propolis samples from different areas of Iran (Chenaran, Taleghan, Morad Beyg, and Kalaleh) with various climates and flora. Methods: ethanolic (70% EtOH) and dichlromethane (DCM) extracts of Iranian propolis were analyzed by gas chromatography-mass spectrometry (GC-MS) methods, and antimicrobial activity was evaluated against Candida albicans, Escherichia coli, and Staphylococcus aureus using disk diffusion antimicrobial method...
May 31, 2017: Iranian Biomedical Journal
https://www.readbyqxmd.com/read/28558334/design-synthesis-and-evaluation-of-aromatic-heterocyclic-derivatives-as-potent-antifungal-agents
#17
Shizhen Zhao, Xiangqian Zhang, Peng Wei, Xin Su, Liyu Zhao, Mengya Wu, Chenzhou Hao, Chunchi Liu, Dongmei Zhao, Maosheng Cheng
To further enhance the anti-Aspergillus efficacy of our previously discovered antifungal lead compounds (1), a series of aromatic heterocyclic derivatives were designed, synthesized and evaluated for in vitro antifungal activity. Many of the target compounds showed good inhibitory activity against Candida albicans and Cryptococcus neoformans. In particular, the isoxazole nuclei were more suited for improving the activity against Aspergillus spp. Among these compounds, 2-F substituted analogues 23g and 23h displayed the most remarkable in vitro activity against Candida spp...
May 24, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28552788/solasodine-3-o-%C3%AE-d-glucopyranoside-kills-candida-albicans-by-disrupting-the-intracellular-vacuole
#18
Wenqiang Chang, Ying Li, Ming Zhang, Sha Zheng, Yan Li, Hongxiang Lou
The increasing incidence of fungal infections and emergence of drug resistance underlie the constant search for new antifungal agents and exploration of their modes of action. The present study aimed to investigate the antifungal mechanisms of solasodine-3-O-β-d-glucopyranoside (SG) isolated from the medicinal plant Solanum nigrum L. In vitro, SG displayed potent fungicidal activity against both azole-sensitive and azole-resistant Candida albicans strains in Spider medium with its MICs of 32 μg/ml. Analysis of structure and bioactivity revealed that both the glucosyl residue and NH group were required for SG activity...
May 25, 2017: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/28549824/the-hsp90-chaperone-network-modulates-candida-virulence-traits
#19
REVIEW
Teresa R O'Meara, Nicole Robbins, Leah E Cowen
Hsp90 is a conserved molecular chaperone that facilitates the folding and function of client proteins. Hsp90 function is dynamically regulated by interactions with co-chaperones and by post-translational modifications. In the fungal pathogen Candida albicans, Hsp90 enables drug resistance and virulence by stabilizing diverse signal transducers. Here, we review studies that have unveiled regulators of Hsp90 function, as well as downstream effectors that govern the key virulence traits of morphogenesis and drug resistance...
May 23, 2017: Trends in Microbiology
https://www.readbyqxmd.com/read/28545374/modulators-of-the-efflux-pump-cdr1p-of-candida-albicans-mechanisms-of-action-and-chemical-features
#20
Viet-Khoa Tran-Nguyen, Rajendra Prasad, Pierre Falson, Ahcène Boumendjel
The multicomponent primary active ATP-binding cassette transporter Cdr1p in the structure of the pathogenic yeast Candida albicans is among the culprits of antifungal agent resistance reported in recent decades. So far, various potential novel inhibitors/ modulators of this protein have been purified, synthesized, and biologically tested, with results showing their ability to effectively reverse CaCdr1p-mediated drug resistance phenomenon. These compounds are of diverse origins, possess non-identical structural features and adopt different mechanisms of action...
May 22, 2017: Current Medicinal Chemistry
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