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https://www.readbyqxmd.com/read/29894182/sterol-14%C3%AE-demethylase-structure-based-design-of-vni-r-n-1-2-4-dichlorophenyl-2-1-h-imidazol-1-yl-ethyl-4-5-phenyl-1-3-4-oxadiazol-2-yl-benzamide-derivatives-to-target-fungal-infections-synthesis-biological-evaluation-and-crystallographic-analysis
#1
Laura Friggeri, Tatiana Y Hargrove, Zdzislaw Wawrzak, Anna L Blobaum, Girish Rachakonda, Craig W Lindsley, Fernando Villalta, W David Nes, Maurizio Botta, F Peter Guengerich, Galina I Lepesheva
Because of the increase in the number of immunocompromised patients, the incidence of invasive fungal infections is growing, but the treatment efficiency remains unacceptably low. The most potent clinical systemic antifungals (azoles) are the derivatives of two scaffolds: ketoconazole and fluconazole. Being the safest antifungal drugs, they still have shortcomings, mainly because of pharmacokinetics and resistance. Here, we report the successful use of the target fungal enzyme, sterol 14α-demethylase (CYP51), for structure-based design of novel antifungal drug candidates by minor modifications of VNI [( R)- N-(1-(2,4-dichlorophenyl)-2-(1 H-imidazol-1-yl)ethyl)-4-(5-phenyl-1,3,4-oxadiazol-2-yl)benzamide)], an inhibitor of protozoan CYP51 that cures Chagas disease...
July 12, 2018: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29883489/mlst-reveals-a-clonal-population-structure-for-cryptococcus-neoformans-molecular-type-vni-isolates-from-clinical-sources-in-amazonas-northern-brazil
#2
Diego Fernando Silva Rocha, Katia Santana Cruz, Carla Silvana da Silva Santos, Lizandra Stephanny Fernandes Menescal, João Ricardo da Silva Neto, Silviane Bezerra Pinheiro, Lucyane Mendes Silva, Luciana Trilles, João Vicente Braga de Souza
Cryptococcosis is considered endemic in Amazonas state, occurring more frequently in individuals with AIDS, who are predominantly infected by Cryptococcus neoformans molecular type VNI. Infections by Cryptococcus gattii VGII predominate in immunocompetent hosts from the American continent and are associated with outbreaks in North America, particularly the subtypes VGIIa and VGIIb, which are also present in the Brazilian Amazon region. Despite few environmental studies, several aspects of the molecular epidemiology of this disease in Amazonas remain unclear, including the limited use of multilocus sequence typing (MLST) to evaluate the genetic population structure of clinical isolates, mainly C...
2018: PloS One
https://www.readbyqxmd.com/read/29762748/molecular-type-specific-multiplex-pcr-produces-a-distinct-vnii-pcr-pattern-among-cryptococcus-neoformans-species-complex
#3
Massimo Cogliati, Mala Rakoto Andrianarivelo, Mohamed Ellabib, Emmanuel N Nnadi, Muriel Cornet
Prevalence of molecular type VNII among Cryptococcus neoformans species complex is probably underestimated since it can be distinguished from VNI only using molecular typing methods such as URA5-RFLP, AFLP, MLST, or whole genome sequencing. Previously, we described a multiplex polymerase chain reaction (PCR) method able to identify VNI, VNIV, and VNIII hybrids, but, at that time, VNII molecular type was not described yet. In this study, 16 VNII global isolates were analyzed by our multiplex PCR method, and results showed that it was able to produce a specific pattern for all the studied VNII isolates, which was different from those of VNI, VNIV, and VNIII...
May 14, 2018: Medical Mycology: Official Publication of the International Society for Human and Animal Mycology
https://www.readbyqxmd.com/read/29740480/estimating-the-intra-taxa-diversity-population-genetic-structure-and-evolutionary-pathways-of-cryptococcus-neoformans-and-cryptococcus-gattii
#4
Marina Muñoz, Milena Camargo, Juan D Ramírez
Members of the Cryptococcus complex, includes Cryptococcus neoformans (most common fungal infection of the brain) and Cryptococcus gattii (high-impact emerging pathogen worldwide). Currently, the fungal multilocus sequence typing database (Fungal MLST Database) constitutes a valuable data repository of the genes used for molecular typing of these pathogens. We analyzed the data available in the Fungal MLST Database for seven housekeeping genes, with the aim to evaluate its contribution in the description of intra-taxa diversity, population genetic structure, and evolutionary patterns...
2018: Frontiers in Genetics
https://www.readbyqxmd.com/read/29712729/conservation-of-intracellular-pathogenic-strategy-among-distantly-related-cryptococcal-species
#5
Joudeh B Freij, Man Shun Fu, Carlos M De Leon Rodriguez, Amanda Dziedzic, Anne E Jedlicka, Quigly Dragotakes, Diego C P Rossi, Eric H Jung, Carolina Coelho, Arturo Casadevall
The genus Cryptococcus includes several species pathogenic for humans. Until recently, the two major pathogenic species were recognized to be Cryptococcus neoformans and Cryptococcus gattii We compared the interaction of murine macrophages with three C. gattii species complex strains (WM179, R265, and WM161, representing molecular types VGI, VGIIa, and VGIII, respectively) and one C. neoformans species complex strain (H99, molecular type VNI) to ascertain similarities and differences in the yeast intracellular pathogenic strategy...
July 2018: Infection and Immunity
https://www.readbyqxmd.com/read/29611304/tuning-surface-electronic-configuration-of-nife-ldhs-nanosheets-by-introducing-cation-vacancies-fe-or-ni-as-highly-efficient-electrocatalysts-for-oxygen-evolution-reaction
#6
Yanyong Wang, Man Qiao, Yafei Li, Shuangyin Wang
Intrinsically inferior electrocatalytic activity of NiFe layered double hydroxides (LDHs) nanosheets is considered as a limiting factor to inhibit the electrocatalytic properties for oxygen evolution reaction (OER). Proper defect engineering to tune the surface electronic configuration of electrocatalysts may significantly improve the intrinsic activity. In this work, the selective formation of cation vacancies in NiFe LDHs nanosheets is successfully realized. The as-synthesized NiFe LDHs-VFe and NiFe LDHs-VNi electrocatalysts show excellent activity for OER, mainly attributed to the introduction of rich iron or nickel vacancies in NiFe LDHs nanosheets, which efficiently tune the surface electronic structure increasing the adsorbing capacity of OER intermediates...
April 2018: Small
https://www.readbyqxmd.com/read/29505557/genotypic-analysis-of-clinical-and-environmental-cryptococcus-neoformans-isolates-from-brazil-reveals-the-presence-of-vnb-isolates-and-a-correlation-with-biological-factors
#7
Leonardo Euripedes Andrade-Silva, Kennio Ferreira-Paim, Thatiana Bragine Ferreira, Anderson Vilas-Boas, Delio José Mora, Verônica Morais Manzato, Fernanda Machado Fonseca, Kelli Buosi, Juliana Andrade-Silva, Bruno da Silva Prudente, Natalia Evelyn Araujo, Helioswilton Sales-Campos, Marcus Vinicius da Silva, Virmondes Rodrigues Júnior, Wieland Meyer, Mario Léon Silva-Vergara
Cryptococcal infections are mainly caused by members of the Cryptococcus neoformans species complex (molecular types VNI, VNII, VNB, VNIV and the AD hybrid VNIII). PCR of the mating type loci and MLST typing using the ISHAM-MLST consensus scheme were used to evaluate the genetic relationship of 102 (63 clinical and 39 environmental) C. neoformans isolates from Uberaba, Brazil and to correlate the obtained genotypes with clinical, antifungal susceptibility and virulence factor data. All isolates were mating type alpha...
2018: PloS One
https://www.readbyqxmd.com/read/29494502/cryptococcosis-in-colombia-compilation-and-analysis-of-data-from-laboratory-based-surveillance
#8
Patricia Escandón, Jairo Lizarazo, Clara Inés Agudelo, Elizabeth Castañeda
The passive and voluntary surveillance of cryptococcosis in Colombia since 1997 has seen an increasing participating rate, revealing its importance to both in immunosuppressed and immunocompetent people. The present work details the national data gathered in 1997-2016, through a retrospective analysis of the information collected in the survey. From a total of 1974 cases reported, an overall incidence of 0.23 cases per 100,000 people was found. This incidence rose to 1.1 cases per 1000 people in the Acquired Immunodeficiency Syndrome (AIDS) population...
March 1, 2018: Journal of Fungi (Basel, Switzerland)
https://www.readbyqxmd.com/read/29461182/molecular-characterization-and-antifungal-susceptibility-testing-of-cryptococcus-neoformans-sensu-stricto-from-southern-brazil
#9
Patricia Fernanda Herkert, Jacques F Meis, Gabriel Lucca de Oliveira Salvador, Renata Rodrigues Gomes, Vania Aparecida Vicente, Marisol Dominguez Muro, Rosangela Lameira Pinheiro, Arnaldo Lopes Colombo, Alexandre Vargas Schwarzbold, Carla Sakuma de Oliveira, Marcelo Simão Ferreira, Flávio Queiroz-Telles, Ferry Hagen
PURPOSE: Cryptococcosis is acquired from the environment by the inhalation of Cryptococcus cells and may establish from an asymptomatic latent infection into pneumonia or meningoencephalitis. The genetic diversity of a Cryptococcus neoformans species complex has been investigated by several molecular tools, such as multi-locus sequence typing, amplified fragment length polymorphism (AFLP), restriction fragment length polymorphism and microsatellite analysis. This study aimed to investigate the genotype distributions and antifungal susceptibility profiles of C...
April 2018: Journal of Medical Microbiology
https://www.readbyqxmd.com/read/29373716/epidemiological-trends-of-cryptococcosis-in-italy-molecular-typing-and-susceptibility-pattern-of-cryptococcus-neoformans-isolates-collected-during-a-20-year-period
#10
Massimo Cogliati, Anna Prigitano, Maria Carmela Esposto, Luisa Romanò, Anna Grancini, Alberto Zani, Anna Maria Tortorano
In the present study clinical data and isolates from cases of cryptococcosis recorded during clinical surveys carried out in Italy from 1997 to 2016, were investigated. Molecular typing and antifungal susceptibility testing were performed in order to delineate the epidemiological trend of cryptococcosis in Italy and to define wild-type population for four different antifungal compounds. During the studied period, a total of 302 cases collected from 32 centers of 11 Italian regions were recorded. Analysis of clinical data showed a significant increase of frequency (from 7% to 38%) of cryptococcosis in human immunodeficiency virus (HIV)-negative patients primarily with hematologic malignancies and solid organ transplantations...
January 23, 2018: Medical Mycology: Official Publication of the International Society for Human and Animal Mycology
https://www.readbyqxmd.com/read/29371747/a-convergent-scalable-and-stereoselective-synthesis-of-azole-cyp51-inhibitors
#11
Galina Lepesheva, Plamen Christov, Gary A Sulikowski, Kwangho Kim
The study and development of azole-based CYP51 inhibitors is an active area of research across disciplines of biochemistry, pharmacology and infectious disease. Support of in vitro and in vivo studies require the development of robust asymmetric routes to single enantiomer products of this class of compounds. Herein, we describe a scalable and enantioselective synthesis to VNI and VFV, the two potent inhibitors of protozoan sterol 14α-demethylase (CYP51) that are currently under consideration for clinical trials for Chagas disease...
November 8, 2017: Tetrahedron Letters
https://www.readbyqxmd.com/read/29239912/evaluating-the-effectiveness-of-visual-narrative-illustrations-used-to-teach-pathophysiology-to-undergraduate-nursing-students
#12
Mohamed El Hussein, Vincent Salyers, Joseph Osuji
Nursing students and nurses often struggle with understanding pathophysiology concepts. Seventy-five students participated in two phases of an exploratory study that evaluated knowledge of pathophysiology concepts when taught using an innovation known as "visual narrative illustrations" (VNIs). Students taught using VNIs performed significantly better on a knowledge posttest and commented that the VNI humor and visual images helped them learn complex concepts. Used in combination with other teaching strategies, VNIs enhanced knowledge and understanding of pathophysiology concepts...
March 2018: Nursing Education Perspectives
https://www.readbyqxmd.com/read/29214970/comparative-typing-analyses-of-clinical-and-environmental-strains-of-the-cryptococcus-neoformans-cryptococcus-gattii-species-complex-from-ivory-coast
#13
COMPARATIVE STUDY
Fulgence K Kassi, Virginie Bellet, Pascal Drakulovski, Donika Krasteva, Frédéric Roger, Bedia-Tanoh A Valérie, Touré Aboubakar, Adama Doumbia, Gisèle A Kouakou, Eric Delaporte, Jacques Reynes, William Yavo, Hervé I E Menan, Sebastien Bertout
PURPOSE: The aim of this study was to assess the biotope of the Cryptococcus neoformans/Cryptococcus gattii species complex from Ivory Coast, and clarify the possible epidemiological relationship between environmental and clinical strains. METHODOLOGY: Samples from Eucalyptus camaldulensis (n=136), Mangifera indica (n=13) and pigeon droppings (n=518) were collected from different sites close to the living environment of Ivorian HIV patients with cryptococcosis (n=10, 50 clinical strains)...
January 2018: Journal of Medical Microbiology
https://www.readbyqxmd.com/read/29094040/preliminary-results-indicate-that-inactivated-vaccine-against-paratuberculosis-could-modify-the-course-of-experimental-mycobacterium-bovis-infection-in-calves
#14
Miriam Serrano, Natalia Elguezabal, Iker A Sevilla, María V Geijo, Elena Molina, Ramón A Juste, Joseba M Garrido
Although paratuberculosis (PTB) vaccination has been recognized as an effective tool to control the disease, its use has been limited in countries undergoing bovine tuberculosis (bTB) eradication programs because of its interference with the diagnostic techniques. Due to this restraint, little is known about the effect of vaccinating against PTB on the progression of bTB infection. To assess this topic, an experimental infection was carried out including the following three groups of five calves each: non-vaccinated infected with Mycobacterium bovis (NVI), vaccinated against PTB infected with M...
2017: Frontiers in Veterinary Science
https://www.readbyqxmd.com/read/29054089/molecular-characterization-of-cryptococcus-neoformans-and-cryptococcus-gattii-from-environmental-sources-and-genetic-comparison-with-clinical-isolates-in-apulia-italy
#15
COMPARATIVE STUDY
Maria Teresa Montagna, Antonella De Donno, Giuseppina Caggiano, Francesca Serio, Osvalda De Giglio, Francesco Bagordo, R D'Amicis, Shawn R Lockhart, Massimo Cogliati
The present study investigated the environmental distribution of Cryptococcus neoformans and C. gattii species complex molecular types, mating types and sequence types in Apulia, a region of Southern Italy. A total of 2078 specimens from arboreal and animal sources were analyzed. The percentage of positive samples was similar among both arboreal and animal specimens: 4.2% vs. 5.1% for C. neoformans species complex and 0.6% vs. 1.4% for C. gattii species complex. Molecular typing identified 78 isolates as VNI (76 αA and two aA), one as AD-hybrid αADa, and 16 as VGI aB...
January 2018: Environmental Research
https://www.readbyqxmd.com/read/28968020/-molecular-characterization-of-cryptococcus-neoformans-isolates-from-hiv-patients-guayaquil-ecuador
#16
Sunny Sánchez, Dolores Zambrano, Maylen García, César Bedoya, Carlos Fernández, María Teresa Illnait-Zaragozí
INTRODUCTION: Neurocryptococcosis is an opportunistic fungal infection that represents a high cost in human lives and for the economy of countries. Its causative agent, the Cryptococcus neoformans/Cryptococcus gattii species complex, has a sexual and an asexual phase, four major serotypes and seven molecular varieties with phenotypic, clinical-epidemiological and antifungal susceptibility differences. OBJECTIVE: To characterize by molecular methods clinical isolates of C...
September 1, 2017: Biomédica: Revista del Instituto Nacional de Salud
https://www.readbyqxmd.com/read/28679543/tracing-genetic-exchange-and-biogeography-of-cryptococcus-neoformans-var-grubii-at-the-global-population-level
#17
Johanna Rhodes, Christopher A Desjardins, Sean M Sykes, Mathew A Beale, Mathieu Vanhove, Sharadha Sakthikumar, Yuan Chen, Sharvari Gujja, Sakina Saif, Anuradha Chowdhary, Daniel John Lawson, Vinicius Ponzio, Arnaldo Lopes Colombo, Wieland Meyer, David M Engelthaler, Ferry Hagen, Maria Teresa Illnait-Zaragozi, Alexandre Alanio, Jo-Marie Vreulink, Joseph Heitman, John R Perfect, Anastasia P Litvintseva, Tihana Bicanic, Thomas S Harrison, Matthew C Fisher, Christina A Cuomo
Cryptococcus neoformans var. grubii is the causative agent of cryptococcal meningitis, a significant source of mortality in immunocompromised individuals, typically human immunodeficiency virus/AIDS patients from developing countries. Despite the worldwide emergence of this ubiquitous infection, little is known about the global molecular epidemiology of this fungal pathogen. Here we sequence the genomes of 188 diverse isolates and characterize the major subdivisions, their relative diversity, and the level of genetic exchange between them...
September 2017: Genetics
https://www.readbyqxmd.com/read/28673800/modeling-hcv-cure-after-an-ultra-short-duration-of-therapy-with-direct-acting-agents
#18
Ashish Goyal, Yoav Lurie, Eric G Meissner, Marian Major, Natasha Sansone, Susan L Uprichard, Scott J Cotler, Harel Dahari
BACKGROUND: Cases of sustained-virological response (SVR or cure) after an ultra-short duration (≤27 days) of direct-acting antiviral (DAA)-based therapy, despite HCV being detected at end of treatment (EOT), have been reported. Established HCV mathematical models that predict the treatment duration required to achieve cure do not take into account the possibility that the infectivity of virus produced during treatment might be reduced. The aim of this study was to develop a new mathematical model that considers the fundamental and critical concept that HCV RNA in serum represents both infectious virus (Vi ) and non-infectious virus (Vni ) in order to explain the observation of cure with ultrashort DAA therapy...
August 2017: Antiviral Research
https://www.readbyqxmd.com/read/28614360/comparative-genomics-of-cryptococcus-neoformans-var-grubii-associated-with-meningitis-in-hiv-infected-and-uninfected-patients-in-vietnam
#19
COMPARATIVE STUDY
Jeremy N Day, Seet Qihui, Lam Tuan Thanh, Phan Hai Trieu, Anh Duong Van, Nha Hoang Thu, Tran Thi Hong Chau, Nguyen P H Lan, Nguyen Van Vinh Chau, Philip M Ashton, Guy E Thwaites, Maciej F Boni, Marcel Wolbers, Niranjan Nagarajan, Patrick B O Tan, Stephen Baker
The vast burden of cryptococcal meningitis occurs in immunosuppressed patients, driven by HIV, and is caused by Cryptococcus neoformans var. grubii. We previously reported cryptococcal meningitis in Vietnam arising atypically in HIV uninfected, apparently immunocompetent patients, caused by a single amplified fragment length polymorphism (AFLP) cluster of C. neoformans var. grubii (VNIγ). This variant was less common in HIV infected individuals; it remains unclear why this lineage is associated with apparently immunocompetent patients...
June 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28611159/population-genomics-and-the-evolution-of-virulence-in-the-fungal-pathogen-cryptococcus-neoformans
#20
Christopher A Desjardins, Charles Giamberardino, Sean M Sykes, Chen-Hsin Yu, Jennifer L Tenor, Yuan Chen, Timothy Yang, Alexander M Jones, Sheng Sun, Miriam R Haverkamp, Joseph Heitman, Anastasia P Litvintseva, John R Perfect, Christina A Cuomo
Cryptococcus neoformans is an opportunistic fungal pathogen that causes approximately 625,000 deaths per year from nervous system infections. Here, we leveraged a unique, genetically diverse population of C. neoformans from sub-Saharan Africa, commonly isolated from mopane trees, to determine how selective pressures in the environment coincidentally adapted C. neoformans for human virulence. Genome sequencing and phylogenetic analysis of 387 isolates, representing the global VNI and African VNB lineages, highlighted a deep, nonrecombining split in VNB (herein, VNBI and VNBII)...
July 2017: Genome Research
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