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synthesis of a new peptide-coumarin conjugate: a potential agent against cryptococcosis.antimicrobial peptides (amps) are currently being investigated as potential sources of novel therapeutics against an increasing number of microorganisms resistant to conventional antibiotics. the conjugation of an amp to other bioactive compounds is an interesting approach for the development of new derivatives with increased antimicrobial efficiency and broader spectra of action. in this work, the synthesis of a new peptide-coumarin conjugate via copper(i)-catalyzed azide-alkyne cycloaddition i ...201525815145
molecular characterisation of clinical cryptococcus neoformans and cryptococcus gattii isolates from sichuan province, china.previous reports on the molecular characteristics of clinical isolates of cryptococcus species in china have focused on isolates from southeast china. to obtain a more detailed molecular epidemiology, a total of 92 cryptococcal isolates were collected from sichuan province. a total of 24 isolates from 12 other provinces were collected for comparative study. genotypes and mating types of 116 cryptococcus isolates were determined. among the 116 isolates, 43 isolates (19 isolates from sichuan and 2 ...201525808662
cryptococcal osteomyelitis in an adolescent survivor of t-cell acute lymphoblastic leukemia.cryptococcosis is infrequent in children, and isolated cryptococcal osteomyelitis is rarely encountered. here, we describe a 14-year-old patient in remission from t-cell acute lymphoblastic leukemia with osteomyelitis because of cryptococcus neoformans var. grubii. the patient was effectively treated with antifungal therapy.201525806844
effects of radiation type and delivery mode on a radioresistant eukaryote cryptococcus neoformans.most research on radioresistant fungi, particularly on human pathogens such as cryptococcus neoformans, involves sparsely-ionizing radiation. consequently, fungal responses to densely-ionizing radiation, which can be harnessed to treat life-threatening fungal infections, remain incompletely understood.201525800676
cytokine profiles at admission can be related to outcome in aids patients with cryptococcal meningitis.cryptococcal meningitis (cm) remains as common life-threatening aids-defining illness mainly in resource-limited settings. previous reports suggested that baseline cytokine profiles can be associated to fungal burden and clinical outcome. this study aimed to evaluate the baseline cytokine profiles in aids patients with cm and its relation with the outcome at weeks 2 and 10. thirty aids patients with cm diagnosed by cerebrospinal fluid (csf) cryptococcus neoformans positive culture, india ink sta ...201525799044
variable region identical iga and ige to cryptococcus neoformans capsular polysaccharide manifest specificity differences.in recent years several groups have shown that isotype switching from igm to igg to iga can affect the affinity and specificity of antibodies sharing identical variable (v) regions. however, whether the same applies to ige is unknown. in this study we compared the fine specificity of v region-identical ige and iga to cryptococcus neoformans capsular polysaccharide and found that these differed in specificity from each other. the ige and iga paratopes were probed by nuclear magnetic resonance spe ...201525778397
in vitro susceptibility testing of amphotericin b for cryptococcus neoformans variety grubii aflp1/vni and cryptococcus gattii aflp6/vgii by clsi and flow cytometry.cryptococcus neoformans var. grubii aflp1/vni is the main causative agent of cryptococcosis associated with aids in the world. cryptococcus gattii aflp6/vgii causes mainly endemic primary infection in immunocompetent hosts. to determine the minimum inhibitory concentrations (mics) of c. neoformans var. grubii aflp1/vni and c. gattii aflp6/vgii against amphotericin b (amb) in a short period of time, flow cytometry (fcm) with fun-1 fluorochrome was used to compare with broth microdilution method ( ...201525756839
cryptococcus neoformans meningitis with negative cryptococcal antigen: evaluation of a new immunochromatographic detection assay.detection of cryptococcal antigen in serum or cerebrospinal fluid allows cryptococcal meningitis diagnosis within few hours with >90% sensitivity. in an hiv-positive patient with cryptococcus neoformans meningitis, initial antigen detection by immunoagglutination was negative. we thus evaluated a new immunochromatographic detection assay that exhibited a higher sensitivity.201525755893
risk factors for invasive cryptococcus neoformans diseases: a case-control study.cryptococcus neoformans is a ubiquitous environmental fungus that can cause life-threatening meningitis and fungemia, often in the presence of acquired immunodeficiency syndrome (aids), liver cirrhosis, diabetes mellitus, or other medical conditions. to distinguish risk factors from comorbidities, we performed a hospital-based, density-sampled, matched case-control study.201525747471
lack of il-6 increases blood-brain barrier permeability in fungal meningitis.the pathogenesis of increased blood-brain barrier permeability during cryptococcus meningitis is still largely unknown. interleukin (il-6) is a multifunctional cytokine, and numerous studies have shown that il-6 influences the integrity of the blood-brain barrier. in this study we investigated the role of il-6 in cryptococcus meningitis. first, wild-type or il-6(-/-) mice were injected with cryptococcus neoformans (c. neoformans) and the survival time in both groups was recorded. second, the num ...201525740137
network-assisted genetic dissection of pathogenicity and drug resistance in the opportunistic human pathogenic fungus cryptococcus neoformans.cryptococcus neoformans is an opportunistic human pathogenic fungus that causes meningoencephalitis. due to the increasing global risk of cryptococcosis and the emergence of drug-resistant strains, the development of predictive genetics platforms for the rapid identification of novel genes governing pathogenicity and drug resistance of c. neoformans is imperative. the analysis of functional genomics data and genome-scale mutant libraries may facilitate the genetic dissection of such complex phen ...201525739925
heterologous expression of galbonolide biosynthetic genes in streptomyces coelicolor.the galbonolide antibiotics are non-glycosylated heptaketide 14-membered macrolides. these antibiotics exhibit broad-spectrum fungicidal activities, including against the human pathogen cryptococcus neoformans. previously, galbonolides b and e were isolated from the marine actinomycete streptomyces sp. lz35. by bioinformatics analysis, the putative galbonolide biosynthetic gene cluster, gbn, was identified in the genome of strain lz35. in order to verify that the core genes (gbna-e) are sufficie ...201525735435
crystal structure of gib2, a signal-transducing protein scaffold associated with ribosomes in cryptococcus neoformans.the atypical gβ-like/rack1 gib2 protein promotes camp signalling that plays a central role in regulating the virulence of cryptococcus neoformans. gib2 contains a seven-bladed β transducin structure and is emerging as a scaffold protein interconnecting signalling pathways through interactions with various protein partners. here, we present the crystal structure of gib2 at a 2.2-å resolution. the structure allows us to analyse the association between gib2 and the ribosome, as well as to identify ...201525732347
the endosomal sorting complex required for transport machinery influences haem uptake and capsule elaboration in cryptococcus neoformans.iron availability is a key determinant of virulence in the pathogenic fungus cryptococcus neoformans. previous work revealed that the escrt (endosomal sorting complex required for transport) protein vps23 functions in iron acquisition, capsule formation and virulence. here, we further characterized the escrt machinery to demonstrate that defects in the escrt-ii and iii complexes caused reduced capsule attachment, impaired growth on haem and resistance to non-iron metalloprotoporphyrins. the escr ...201525732100
long-term survival of cryptococcus neoformans and cryptococcus gattii in stored environmental samples from colombia.both cryptococcus neoformans and cryptococcus gattii have been isolated from a variety of environmental sources in colombia.201525725529
successful treatment of cryptococcus neoformans immune reconstitution inflammatory syndrome in an immunocompetent host using thalidomide.immune reconstitution inflammatory syndrome (iris) can complicate antifungal treatment of cryptococcosis. there are limited data on managing cryptococcal-associated iris. we describe an immunocompetent patient who developed iris complicating cryptococcus neoformans meningitis, successfully treated with thalidomide following failure of corticosteroid therapy. data on thalidomide use in cryptococcal iris are awaited.201527330941
report of filamentous forms in a mating type vni clinical sequential isolates of cryptococcus neoformans from an hiv virus-infected patient.we reported a cryptococcal meningitis aids-patient infected with a mating type vni isolate showing filamentous cells in direct examination of cerebrospinal fluid. clinical data, outcome, treatment features and microbiological findings were discussed.201527330939
targeting the cryptococcus neoformans var. grubii cell wall using lectins: study of the carbohydrate-binding domain.cryptococcus neoformans var. grubii is considered to be the major cause of cryptococcosis in immunosuppressed patients. understanding cell wall glycoproteins using lectins is of medical interest and can contribute to specific therapy. the aim of this study was to evaluate the carbohydrates on the cell wall of cryptococcus neoformans var. grubii clinical isolates, using a fluorescein isothiocyanate-lectin binding protocol. thirty yeast strains stocked in the culture collection were cultivated for ...201525723851
primary cutaneous cryptococcosis treated with debridement and fluconazole monotherapy in an immunosuppressed patient: a case report and review of the literature.cryptococcus neoformans is an opportunistic yeast present in the environment. practitioners are familiar with the presentation and management of the most common manifestation of cryptococcal infection, meningoencephalitis, in patients with aids or other conditions of immunocompromise. there is less awareness, however, of uncommon presentations where experience rather than evidence guides therapy. we report a case of primary cutaneous cryptococcosis (pcc) in a patient who had been immunosuppresse ...201525722900
recognition of seven species in the cryptococcus gattii/cryptococcus neoformans species complex.phylogenetic analysis of 11 genetic loci and results from many genotyping studies revealed significant genetic diversity with the pathogenic cryptococcus gattii/cryptococcus neoformans species complex. genealogical concordance, coalescence-based, and species tree approaches supported the presence of distinct and concordant lineages within the complex. consequently, we propose to recognize the current c. neoformans var. grubii and c. neoformans var. neoformans as separate species, and five specie ...201525721988
histone deacetylases inhibitors effects on cryptococcus neoformans major virulence phenotypes.cryptococcus neoformans undergoes phenotypical changes during host infection in order to promote persistence and survival. studies have demonstrated that such adaptations require alterations in gene transcription networks by distinct mechanisms. drugs such as the histone deacetylases inhibitors (hdaci) sodium butyrate (nabut) and trichostatin a (tsa) can alter the chromatin conformation and have been used to modulate epigenetic states in the treatment of diseases such as cancer. in this work, we ...201526103530
the morphotype heterogeneity in cryptococcus neoformans.many environmental fungi have evolved exceptional abilities to overcome host defenses and to cause systemic infections. however, the evolutionary trajectory that gives rise to the remarkable pathogenic traits of otherwise saprophytic species is poorly understood. recent studies suggest that social behaviors likely enhance fitness and augment virulence in the ubiquitous fungus cryptococcus neoformans. in this regard, heterogeneity in morphotypes and the ability to switch morphotype offer flexibil ...201526094087
is development of a vaccine against cryptococcus neoformans feasible? 201526087178
[study on genotype and virulence of cryptococcus neoformans and cryptococcus gattii clinical isolates in guigang, guangxi zhuang autonomous region].to understand the species, genotypes and mating types of cryptococcus neoformans and cryptococcus gattii isolated from clinical samples in guigang, guangxi zhuang autonomous region.201526080640
clinical analysis of pulmonary cryptococcosis in non-hiv patients in south china.the aim of this study was to investigate the clinical characteristics of pulmonary cryptococcosis occurring in non-hiv patients, and to develop early diagnosis of pulmonary cryptococcosis in immunocompetent cases as well.201526064200
cryptococcosis serotypes impact outcome and provide evidence of cryptococcus neoformans speciation.cryptococcus neoformans is a human opportunistic fungal pathogen causing severe disseminated meningoencephalitis, mostly in patients with cellular immune defects. this species is divided into three serotypes: a, d, and the ad hybrid. our objectives were to compare population structures of serotype a and d clinical isolates and to assess whether infections with ad hybrids differ from infections with the other serotypes. for this purpose, we analyzed 483 isolates and the corresponding clinical dat ...201526060271
comparative analyses of clinical and environmental populations of cryptococcus neoformans in botswana.cryptococcus neoformans var. grubii (cng) is the most common cause of fungal meningitis, and its prevalence is highest in sub-saharan africa. patients become infected by inhaling airborne spores or desiccated yeast cells from the environment, where the fungus thrives in avian droppings, trees and soil. to investigate the prevalence and population structure of cng in southern africa, we analysed isolates from 77 environmental samples and 64 patients. we detected significant genetic diversity amon ...201526053414
fungal inositol pyrophosphate ip7 is crucial for metabolic adaptation to the host environment and pathogenicity.inositol pyrophosphates (pp-ips) comprising inositol, phosphate, and pyrophosphate (pp) are essential for multiple functions in eukaryotes. their role in fungal pathogens has never been addressed. cryptococcus neoformans is a model pathogenic fungus causing life-threatening meningoencephalitis. we investigate the cryptococcal kinases responsible for the production of pp-ips (ip7/ip8) and the hierarchy of pp-ip importance in pathogenicity. using gene deletion and inositol polyphosphate profiling, ...201526037119
antimicrobial activity of β-lapachone encapsulated into liposomes against meticillin-resistant staphylococcus aureus and cryptococcus neoformans clinical strains.the aim of this study was to determine whether encapsulation of β-lapachone (β-lap) into liposomes interferes with its in vitro antimicrobial activity against meticillin-resistant staphylococcus aureus (mrsa) and cryptococcus neoformans clinical strains. liposomes (β-lap:lipo or β-lap:hpβ-cd-lipo) were prepared using the hydration of thin lipid film method followed by sonication. the in vitro antimicrobial activities of β-lap-loaded liposomes against mrsa and c. neoformans were evaluated using t ...201527873657
analysis of asthma patients for cryptococcal seroreactivity in an urban german area.cryptococcus neoformans is an opportunistic fungal pathogen that causes lung inflammation and meningoencephalitis in immunocompromised patients but is also able to asymptomatically infect immunocompetent individuals. c. neoformans is found ubiquitously especially in urban areas where it is spread by pigeons, and fungal exposure may predispose for asthma development already at an early age, as soon as confronted with pigeon droppings. in the study presented here, we investigated the presence of s ...201526026172
adaptation strategies: how environmental fungi become fatal?most fungi contributing to systemic human infections are environmental pathogens, whose fatal pathogenicity is largely derived from their survival strategies developed to adapt to a plethora of natural stressors. a well-studied example of such pathogens is cryptococcus neoformans. c. neoformans can cause life-threatening cryptococcosis and meningoencephalitis, which claim more than 600 000 lives annually. recent findings reveal that the coordinated application of strategies like morphotype trans ...201525998431
a synthetic strategy to xylose-containing thioglycoside tri- and tetrasaccharide building blocks corresponding to cryptococcus neoformans capsular polysaccharide structures.as part of an ongoing project aimed at developing vaccine candidates against cryptococcus neoformans the preparation of tri- and tetrasaccharide thioglycoside building blocks, to be used in construction of structurally defined part structures of c. neoformans gxm capsular polysaccharide, was investigated. using a naphthalenylmethyl (nap) ether as a temporary protecting group and trichloroacetimidate donors in optimized glycosylations the target building blocks, ethyl 6-o-acetyl-2,4-di-o-benzyl-3 ...201525986781
disseminated cryptococcal infection in an immunocompetent host mimicking plasma cell disorder: a case report and literature review.cryptococcosis is a potentially fatal fungal infection caused mainly by cryptocococcus neoformans (cn) species and it rarely infects immunocompetent hosts. the outcomes are better only if the condition is suspected and diagnosed early and treatment is instituted.201525984313
rising to the challenge of multiple cryptococcus species and the diseases they cause.cryptococcus neoformans and cryptococcus gattii are well-studied basidiomyceteous yeasts that are capable of causing disease in healthy and immunocompromised people. the conference on cryptococcus and cryptococcosis (iccc) is held every three years: the accompanying special issue stems from the 9th iccc and covers a subset of the topics related to these fungi in detail. this conference started with a revised and reduced estimate of disease burden globally, in part due to improved treatment for h ...201525983191
cryptococcal heat shock protein 70 homolog ssa1 contributes to pulmonary expansion of cryptococcus neoformans during the afferent phase of the immune response by promoting macrophage m2 polarization.numerous virulence factors expressed by cryptococcus neoformans modulate host defenses by promoting nonprotective th2-biased adaptive immune responses. prior studies demonstrate that the heat shock protein 70 homolog, ssa1, significantly contributes to serotype d c. neoformans virulence through the induction of laccase, a th2-skewing and cns tropic factor. in the present study, we sought to determine whether ssa1 modulates host defenses in mice infected with a highly virulent serotype a strain o ...201525972480
a single protein s-acyl transferase acts through diverse substrates to determine cryptococcal morphology, stress tolerance, and pathogenic outcome.cryptococcus neoformans is an opportunistic yeast that kills over 625,000 people yearly through lethal meningitis. host phagocytes serve as the first line of defense against this pathogen, but fungal engulfment and subsequent intracellular proliferation also correlate with poor patient outcome. defining the interactions of this facultative intracellular pathogen with host phagocytes is key to understanding the latter's opposing roles in infection and how they contribute to fungal latency, dissem ...201525970403
[cutaneous cryptococcosis mimicking basal cell carcinoma and revealing systemic involvement in acquired immunodeficiency].cryptococcosis is a rare and a serious opportunistic infection that occurs primarily on the field of immunodeficiency. we report a case of disseminated cryptococcosis in acquired immunodeficiency syndrome revealed by unusual skin lesions.201525959736
identification of genes involved in the phosphate metabolism in cryptococcus neoformans.cryptococcus neoformans is a pathogenic basidiomycetous yeast that can cause life-threatening meningoencephalitis in immuno-compromized patients. to propagate in the human body, this organism has to acquire phosphate that functions in cellular signaling pathways and is also an essential component of nucleic acids and phospholipids. thus it is reasonable to assume that c. neoformans (cn) possesses a phosphate regulatory system (pho system) analogous to that of other fungi. by blast searches using ...201525957252
decreased tlr2 signal expression in peripheral blood mononuclear cell from patients with cryptococcal meningitis.toll-like receptors are the most important pattern recognition receptors that can recognize conserved molecular structures shared by large groups of pathogens. here, the aim was to determine the expression and role of tlr2 in peripheral blood mononuclear cells (pbmcs) from patients with cryptococcal meningitis and healthy controls. tlr2 expression was measured using rt-pcr and western blotting. the role of tlr2 in cytokine production by pbmcs after cryptococcus neoformans exposure was assessed i ...201525951991
isavuconazole: a new option for the management of invasive fungal infections.to review the pharmacology, chemistry, in vitro susceptibility, pharmacokinetics, clinical efficacy, safety, tolerability, dosage, and administration of isavuconazole, a triazole antifungal agent.201525940222
antioxidant and antimycotic activities of two native lavandula species from portugal.the antioxidant and antimycotic activities of the essential oils and extracts of two native portuguese lavandula species, l. stoechas subsp. luisieri and l. pedunculata, were evaluated by in vitro assays. the total phenolics and flavonoids content were also determined. the antioxidant potential was assessed through dpph radical scavenging, inhibition of lipid peroxidation (ilp), and dna protection assays. all samples displayed a high dpph scavenging activity, some of them showing concentration d ...201525922611
primary capsule-deficient cutaneous cryptococcosis in a sporotrichoid pattern in an immunocompetent host.cryptococcosis is an opportunistic yeast infection caused by cryptococcus neoformans that remains the most common systemic fungal infection in immunosuppressed patients and often presents with signs of meningitis. primary cutaneous cryptococcosis (pcc) is a more rare clinical identity that is characterized by skin lesions confined to 1 body region, often presenting as a whitlow or phlegmon with positive culture for c neoformans and no evidence of simultaneous dissemination. we report a rare case ...201526244363
selection of orthologous genes for construction of a highly resolved phylogenetic tree and clarification of the phylogeny of trichosporonales species.the order trichosporonales (tremellomycotina, basidiomycota) includes various species that have clinical, agricultural and biotechnological value. thus, understanding why and how evolutionary diversification occurred within this order is extremely important. this study clarified the phylogenetic relationships among tricosporonales species. to select genes suitable for phylogenetic analysis, we determined the draft genomes of 17 trichosporonales species and extracted 30 protein-coding dna sequenc ...201526241762
from the blood to the brain: avenues of eukaryotic pathogen dissemination to the central nervous system.infection of the central nervous system (cns) is a significant cause of morbidity and mortality, and treatments available to combat the highly debilitating symptoms of cns infection are limited. the mechanisms by which pathogens in the circulation overcome host immunity and breach the blood-brain barrier are active areas of investigation. in this review, we discuss recent work that has significantly advanced our understanding of the avenues of pathogen dissemination to the cns for four eukaryoti ...201526048316
[role of cd44 in monocyte transmigration across cryptococcus neoformans-infected blood-brain barrier in vitro].to explore the role of cd44 in monocyte adhesion to human brain microvascular endothelial cells (hbmecs) and monocyte migration across an in vitro model of blood-brain barrier (bbb) infected by cryptococcus neoformans (cn).201525907927
the granuloma response controlling cryptococcosis in mice depends on the sphingosine kinase 1-sphingosine 1-phosphate pathway.cryptococcus neoformans is a fungal pathogen that causes pulmonary infections, which may progress into life-threatening meningitis. in commonly used mouse models of c. neoformans infections, fungal cells are not contained in the lungs, resulting in dissemination to the brain. we have previously reported the generation of an engineered c. neoformans strain (c. neoformans δgcs1) which can be contained in lung granulomas in the mouse model and have shown that granuloma formation is dependent upon t ...201525895971
biolistic transformation of a fluorescent tagged gene into the opportunistic fungal pathogen cryptococcus neoformans.the basidiomycete cryptococcus neoformans, an invasive opportunistic pathogen of the central nervous system, is the most frequent cause of fungal meningitis worldwide resulting in more than 625,000 deaths per year worldwide. although electroporation has been developed for the transformation of plasmids in cryptococcus, only biolistic delivery provides an effective means to transform linear dna that can be integrated into the genome by homologous recombination.  acetate has been shown to be a maj ...201525867491
host immunity to cryptococcus neoformans.cryptococcosis is caused by the fungal genus cryptococcus. cryptococcosis, predominantly meningoencephalitis, emerged with the hiv pandemic, primarily afflicting hiv-infected patients with profound t-cell deficiency. where in use, combination antiretroviral therapy has markedly reduced the incidence of and risk for disease, but cryptococcosis continues to afflict those without access to therapy, particularly in sub-saharan africa and asia. however, cryptococcosis also occurs in solid organ trans ...201525865194
impact of protein palmitoylation on the virulence potential of cryptococcus neoformans.the localization and specialized function of ras-like proteins are largely determined by posttranslational processing events. in a highly regulated process, palmitoyl groups may be added to c-terminal cysteine residues, targeting these proteins to specific membranes. in the human fungal pathogen cryptococcus neoformans, ras1 protein palmitoylation is essential for growth at high temperature but is dispensable for sexual differentiation. ras1 palmitoylation is also required for localization of th ...201525862155
a genomic safe haven for mutant complementation in cryptococcus neoformans.just as koch's postulates formed the foundation of early infectious disease study, stanley falkow's molecular koch's postulates define best practice in determining whether a specific gene contributes to virulence of a pathogen. fundamentally, these molecular postulates state that if a gene is involved in virulence, its removal will compromise virulence. likewise, its reintroduction should restore virulence to the mutant. these approaches are widely employed in cryptococcus neoformans, where gene ...201525856300
systematic functional profiling of transcription factor networks in cryptococcus neoformans.cryptococcus neoformans causes life-threatening meningoencephalitis in humans, but its overall biological and pathogenic regulatory circuits remain elusive, particularly due to the presence of an evolutionarily divergent set of transcription factors (tfs). here, we report the construction of a high-quality library of 322 signature-tagged gene-deletion strains for 155 putative tf genes previously predicted using the dna-binding domain tf database, and examine their in vitro and in vivo phenotypic ...201525849373
clinical features and hematopoietic stem cell transplantations for cd40 ligand deficiency in japan.the long-term outcome of x-linked hyper-igm syndrome (xhim) caused by mutations in cd40lg is poor, and the only curative treatment is hematopoietic stem cell transplantation (hsct).201525840720
genetic and pathological characteristics of cryptococcus gattii and cryptococcus neoformans var. neoformans from meningoencephalitis in autochthonous goats and mouflons, sardinia, italy.in this study, we examined in sardinia the brain of 555 autochthonous sheep, 50 goats, and 4 mouflons which were found affected by neurological signs. we found 6 goats and one mouflon with meningoencephalitis caused by cryptococcus sp. there was no evidence of cryptococcal infections in any of the examined sheep. mlst genotyping on cryptococcus sp. isolates identified cryptococcus gatti genotype aflp4/vgi and cryptococcus neoformans var. neoformans genotype aflp2/vniv. phylogenetically, all cryp ...201525840469
evaluation of fingerstick cryptococcal antigen lateral flow assay in hiv-infected persons: a diagnostic accuracy study.cryptococcus neoformans is the most common cause of adult meningitis in sub-saharan africa. the cryptococcal antigen (crag) lateral flow assay (lfa) has simplified diagnosis as a point-of-care test approved for serum or cerebrospinal fluid (csf). we evaluated the accuracy of the crag lfa using fingerstick whole blood compared with serum/plasma and csf for diagnosing meningitis.201525838287
cryptococcus neoformans host adaptation: toward biological evidence of dormancy.cryptococcosis is an opportunistic infection due to the ubiquitous yeast cryptococcus neoformans. this yeast interacts closely with innate immune cells, leading to various fates, including fungal persistence within cells, making possible the dissemination of the yeast cells with monocytes via a trojan horse strategy. in humans, the natural history of the infection begins with primoinfection during childhood, which is followed by dormancy and, in some individuals, reactivation upon immunosuppress ...201525827423
essential gene discovery in the basidiomycete cryptococcus neoformans for antifungal drug target prioritization.fungal diseases represent a major burden to health care globally. as with other pathogenic microbes, there is a limited number of agents suitable for use in treating fungal diseases, and resistance to these agents can develop rapidly. cryptococcus neoformans is a basidiomycete fungus that causes cryptococcosis worldwide in both immunocompromised and healthy individuals. as a basidiomycete, it diverged from other common pathogenic or model ascomycete fungi more than 500 million years ago. here, w ...201525827419
[cryptococcal meningitis].immunocompromised patients are at increased risk of disseminated cryptococcal infection, often presenting as a primary respiratory infection with yeast cells originating from bird excreta. because cryptococcus neoformans has a tropism for cerebrospinal fluid, most patients suffer from meningitis or meningoencephalitis. symptoms of cryptococcal meningitis are non-specific: headache, fever, nausea, or altered mental state and behaviour. case descriptions of a renal transplant recipient and an hiv ...201525827149
solid-state nmr reveals the carbon-based molecular architecture of cryptococcus neoformans fungal eumelanins in the cell wall.melanin pigments protect against both ionizing radiation and free radicals and have potential soil remediation capabilities. eumelanins produced by pathogenic cryptococcus neoformans fungi are virulence factors that render the fungal cells resistant to host defenses and certain antifungal drugs. because of their insoluble and amorphous characteristics, neither the pigment bonding framework nor the cellular interactions underlying melanization of c. neoformans have yielded to comprehensive molecu ...201525825492
cryptococcal panniculitis in a renal transplant recipient: case report and review of literature.cryptococcosis is a deep fungal infection caused by cryptococcus neoformans. the infection usually involves the lungs, the central nervous system as well as the skin, the bones and the urinary tract. immunocompromised individuals, including solid organ transplant recipients, are at higher risk for cryptococcal infections.201526512304
hyponatremia as the initial presentation of cryptococcal meningitis after liver transplantation.meningoencephalitis is the most common clinical manifestation of cryptococcal infection, as the organism has a propensity to invade the cns. patients often present with elevated intracranial pressure, focal motor deficits, altered mentation and internal hydrocephalus. syndrome of inappropriate antidiuretic hormone secretion (siadh) has been reported as a notable cause of euvolemic hyponatremia in immunocompromised patients.201526504469
real-time imaging of interactions of neutrophils with cryptococcus neoformans demonstrates a crucial role of complement c5a-c5ar signaling.neutrophils have been shown to efficiently kill cryptococcus neoformans, a causative agent of meningoencephalitis. here, using live-cell imaging, we characterize the dynamic interactions of neutrophils with c. neoformans and the underlying mechanisms in real time. neutrophils were directly seen to chase c. neoformans cells and then rapidly internalize them. complement c5a-c5ar signaling guided neutrophils to migrate to the yeast cells, resulting in optimal phagocytosis and subsequent killing of ...201526502909
commentary: role of sterylglucosidase 1 (sgl1) on the pathogenicity of cryptococcus neoformans: potential applications for vaccine development. 201526500643
dark chemical matter as a promising starting point for drug lead discovery.high-throughput screening (hts) is an integral part of early drug discovery. herein, we focused on those small molecules in a screening collection that have never shown biological activity despite having been exhaustively tested in hts assays. these compounds are referred to as 'dark chemical matter' (dcm). we quantified dcm, validated it in quality control experiments, described its physicochemical properties and mapped it into chemical space. through analysis of prospective reporter-gene assay ...201526479441
internalized cryptococcus neoformans activates the canonical caspase-1 and the noncanonical caspase-8 inflammasomes.cryptococcus neoformans is an opportunistic fungal pathogen that causes cryptococcosis in immunocompromised patients as well as immunocompetent individuals. host cell surface receptors that recognize c. neoformans have been widely studied. however, intracellular sensing of this pathogen is still poorly understood. our previous studies have demonstrated that both biofilm and acapsular mutant of c. neoformans are able to activate the nod-like receptor family, pyrin domain-containing 3 (nlrp3) infl ...201526466953
the role of host microfilaments and microtubules during opsonin-independent interactions of cryptococcus neoformans with mammalian lung cells.the purpose of this investigation was to characterise the interactions of cryptococcus neoformans with mammalian host alveolar epithelial cells and alveolar macrophages, with emphasis on the roles of the cryptococcal capsule and the host cell cytoskeletons. the adherence and internalisation of c. neoformans into mammalian lung cells and the roles of host cell cytoskeletons in host-pathogen interactions were studied using in vitro models coupled with a differential fluorescence assay, fluorescenc ...201526463450
polyploid titan cells produce haploid and aneuploid progeny to promote stress adaptation.cryptococcus neoformans is a major life-threatening fungal pathogen. in response to the stress of the host environment, c. neoformans produces large polyploid titan cells. titan cell production enhances the virulence of c. neoformans, yet whether the polyploid aspect of titan cells is specifically influential remains unknown. we show that titan cells were more likely to survive and produce offspring under multiple stress conditions than typical cells and that even their normally sized daughters ...201526463162
false-negative cerebrospinal fluid fungal culture results following oral antineoplastic therapy with a 5-fluorouracil derivative.cryptococcus neoformans, a common opportunistic pathogen among patients with human immunodeficiency virus (hiv) infection, lymphoproliferative disorders and other conditions causing immunosuppression, can be differentiated from other yeasts using biochemical tests as well as culture results and direct histopathological examination.201526456089
virulence-associated enzymes of cryptococcus neoformans.enzymes play key roles in fungal pathogenesis. manipulation of enzyme expression or activity can significantly alter the infection process, and enzyme expression profiles can be a hallmark of disease. hence, enzymes are worthy targets for better understanding pathogenesis and identifying new options for combatting fungal infections. advances in genomics, proteomics, transcriptomics, and mass spectrometry have enabled the identification and characterization of new fungal enzymes. this review focu ...201526453651
secretome profiling of cryptococcus neoformans reveals regulation of a subset of virulence-associated proteins and potential biomarkers by protein kinase a.the pathogenic yeast cryptococcus neoformans causes life-threatening meningoencephalitis in individuals suffering from hiv/aids. the cyclic-amp/protein kinase a (pka) signal transduction pathway regulates the production of extracellular virulence factors in c. neoformans, but the influence of the pathway on the secretome has not been investigated. in this study, we performed quantitative proteomics using galactose-inducible and glucose-repressible expression of the pka1 gene encoding the catalyt ...201526453029
cryptococcal meningitis due to cryptococcus neoformans genotype aflp1/vni in iran: a review of the literature.cryptococcal meningitis is the most important opportunistic fungal infection with a high mortality in hiv-patients in less developed regions. here, we report a case of cryptococcal meningitis in a 49-year-old hiv-positive female due to cryptococcus neoformans (serotype a, mating-type alpha, genotype aflp1/vni) in sari, iran. in vitro antifungal susceptibility tests showed mics of isavuconazole (0.016 μg ml(-1) ), voriconazole (0.031 μg ml(-1) ), posaconazole (0.031 μg ml(-1) ), itraconazole (0.0 ...201526444438
development of protective inflammation and cell-mediated immunity against cryptococcus neoformans after exposure to hyphal mutants.morphological switch is tightly coupled with the pathogenesis of many dimorphic fungal pathogens. cryptococcus neoformans, the major causative agent of cryptococcal meningitis, mostly presents as the yeast form but is capable of switching to the hyphal form. the filamentous form has long been associated with attenuated virulence, yet the underlying mechanism remains elusive. we previously identified the master regulator znf2 that controls the yeast-to-hypha transition in cryptococcus. activation ...201526443458
cryptococcus neoformans and streptococcus pneumoniae co-infection in post-traumatic meningitis in a patient with unknown hiv status.meningitis is a serious disease associated with considerable morbidity and mortality. mixed meningeal infections due to bacteria and fungi are exceptionally rare. here we report a case of meningeal co-infection with cryptococcus neoformans and streptococcus pneumoniae in a patient with unknown human immunodeficiency virus status. because of the rarity of such cases, stringent screening of every cerebrospinal fluid specimen to exclude the presence of multiple pathogens is imperative. assessment o ...201526440847
structure of a fungal form of aspartate semialdehyde dehydrogenase from cryptococcus neoformans.aspartate semialdehyde dehydrogenase (asadh) functions at a critical junction in the aspartate-biosynthetic pathway and represents a valid target for antimicrobial drug design. this enzyme catalyzes the nadph-dependent reductive dephosphorylation of β-aspartyl phosphate to produce the key intermediate aspartate semialdehyde. production of this intermediate represents the first committed step in the biosynthesis of the essential amino acids methionine, isoleucine and threonine in fungi, and also ...201526527262
cryptococcosis in atlántico, colombia: an approximation of the prevalence of this mycosis and the distribution of the etiological agent in the environment.cryptococcosis is an invasive disease acquired by inhalation of infectious propagules from the environment. currently, compulsory notification of the spread of this disease is not required in colombia. however, reporting of human immunodeficiency virus (hiv)/acquired immune deficiency syndrome cases to the national surveillance system has suggested that there is a growing population at risk of contracting cryptococcosis. few studies have described the occurrence of cryptococcosis in colombia. th ...201526516968
[cryptococcosis during hiv infection].cryptococcosis is a cosmopolitan fungal serious condition due to an encapsulated yeast cryptococcus neoformans. this is the systemic fungal infection the most common in hiv infection. this yeast is present in the environment and its main entrance in the body is the respiratory tract. its gravity is linked to its tropism for the central nervous system. it generally affects subjects with severe deficit of cellular immunity and in particular, patients living with hiv. the diagnosis of neuromeningea ...201526515783
how cryptococcus interacts with the blood-brain barrier.cryptococcus demonstrates predilection for invasion of the brain, but the mechanism by which cryptococcus crosses the blood-brain barrier (bbb) to cause brain invasion is largely unknown. in order for cryptococcus to cross the bbb, there must be a way to either cross human brain microvascular endothelial cells, which are the main constitute of the bbb, or go in between tight junctions. recent evidence of human brain microvascular endothelial cell responses to transcellular brain invasions includ ...201526437710
direct invasion of the optic nerves, chiasm, and tracts by cryptococcus neoformans in an immunocompetent host.cryptococcus spp is a common fungal infection and frequent cause of meningitis in immunocompromised patients; however, immunocompetent patients are also at risk of infection. visual loss often occurs via elevated intracranial hypertension but can rarely occur through direct optic nerve, chiasm, or tract invasion. we report a case of a 38-year-old woman who presented with decreased acuity in both eyes. she had generalized visual field constriction in the right eye and temporal hemianopsia in the ...201526425249
live imaging of host-parasite interactions in a zebrafish infection model reveals cryptococcal determinants of virulence and central nervous system invasion.the human fungal pathogen cryptococcus neoformans is capable of infecting a broad range of hosts, from invertebrates like amoebas and nematodes to standard vertebrate models such as mice and rabbits. here we have taken advantage of a zebrafish model to investigate host-pathogen interactions of cryptococcus with the zebrafish innate immune system, which shares a highly conserved framework with that of mammals. through live-imaging observations and genetic knockdown, we establish that macrophages ...201526419880
molecular types of cryptococcus gattii/cryptococcus neoformans species complex from clinical and environmental sources in nairobi, kenya.cryptococcal meningitis infections cause high mortality rates among hiv-infected patients in sub-saharan africa. the high incidences of cryptococcal infections may be attributed to common environmental sources which, if identified, could lead to institution of appropriate control strategies. to determine the genotypes of cryptococcus gattii/c. neoformans- species complex from nairobi, kenya, 123 clinical and environmental isolates were characterised. typing was done using orotidine monophosphate ...201526404188
cluster of cryptococcus neoformans infections in intensive care unit, arkansas, usa, 2013. 201526403080
pleural effusion as the initial clinical presentation in disseminated cryptococcosis and fungaemia: an unusual manifestation and a literature review.cryptococcus neoformans infection usually presents as chronic meningitis and is increasingly being recognized in immunocompromised patients. presentation with pleural effusion is rare in cryptococcal disease; in fact, only 4 cases of pleural effusion as the initial clinical presentation in cryptococcosis have been reported in english-language literature to date. we report the first case of pleural effusion as the initial clinical presentation in a renal transplant recipient who was initially mis ...201526395579
prevention of invasive fungal infections in immunocompromised patients: the role of delayed-release posaconazole.posaconazole is a triazole antifungal agent that has broad-spectrum activity against many yeasts and filamentous fungi, including candida species, cryptococcus neoformans, aspergillus species, and zygomycetes. this drug has been approved for the prevention of invasive fungal infections in patients with neutropenia and for the treatment of invasive fungal infections in hematopoietic stem cell transplant recipients with graft-versus-host disease. studies on the clinical efficacy, safety, tolerabil ...201526392781
the cch1-mid1 high-affinity calcium channel contributes to the virulence of cryptococcus neoformans by mitigating oxidative stress.pathogenic fungi have developed mechanisms to cope with stresses imposed by hosts. for cryptococcus spp., this implies active defense mechanisms that attenuate and ultimately overcome the onslaught of oxidative stresses in macrophages. among cellular pathways within cryptococcus neoformans' arsenal is the plasma membrane high-affinity cch1-mid1 calcium (ca(2+)) channel (cmc). here we show that cmc has an unexpectedly complex and disparate role in mitigating oxidative stress. upon inhibiting the ...201526385891
cryptococcus neoformans infection in mice lacking type i interferon signaling leads to increased fungal clearance and il-4-dependent mucin production in the lungs.type i interferons (ifns) are secreted by many cell types upon stimulation via pattern recognition receptors and bind to ifn-α/β receptor (ifnar), which is composed of ifnar1 and ifnar2. although type i ifns are well known as anti-viral cytokines, limited information is available on their role during fungal infection. in the present study, we addressed this issue by examining the effect of ifnar1 defects on the host defense response to cryptococcus neoformans. in ifnar1ko mice, the number of liv ...201526384031
a novel experimental model of cryptococcus neoformans-related immune reconstitution inflammatory syndrome (iris) provides insights into pathogenesis.antiretroviral therapy (art) has yielded major advances in fighting the hiv pandemic by restoring protective immunity. however, a significant proportion of hiv patients co-infected with the opportunistic fungal pathogen cryptococcus neoformans paradoxically develops a life-threatening immune reconstitution inflammatory syndrome (iris) during antiretroviral therapy. despite several clinical studies, the underlying pathomecha-nisms are poorly understood. here, we present the first mouse model of c ...201526381487
cholinesterase of rats experimentally infected by cryptococcus neoformans: relationship between inflammatory response and pathological findings.the aim of this study was to assess the role of the acetylcholinesterase (ache) and butyrylcholinesterase (bche) as biomarkers of inflammation and tissue injury on rats experimentally infected by cryptococcus neoformans. for this purpose, 20 male rats were divided into two groups: 10 animals representing the uninfected control group (group a) and 10 c. neoformans var. grubii infected animals (group b). blood and brain samples were collected on days 10 (a10 and b10), and 30 (a30 and b30) post-inf ...201526376950
lc-ms- and (1)h nmr spectroscopy-guided identification of antifungal diterpenoids from sagittaria latifolia.antifungal screening of small-molecule natural product libraries showed that a column fraction (cf) derived from the plant extract of sagittaria latifolia was active against the fungal pathogen cryptococcus neoformans. dereplication analysis by liquid chromatography-mass spectrometry (lc-ms) and proton nuclear magnetic resonance spectroscopy ((1)h nmr) indicated the presence of new compounds in this cf. subsequent fractionation of the plant extract resulted in the identification of two new isopi ...201526371504
the cnes2 locus on mouse chromosome 17 regulates host defense against cryptococcal infection through pleiotropic effects on host immunity.the genetic basis of natural susceptibility to progressive cryptococcus neoformans infection is not well understood. using c57bl/6 and cba/j inbred mice, we previously identified three chromosomal regions associated with c. neoformans susceptibility (cnes1, cnes2, and cnes3). to validate and characterize the role of cnes2 during the host response, we constructed a congenic strain on the c57bl/6 background (b6.cba-cnes2). phenotypic analysis of b6.cba-cnes2 mice 35 days after c. neoformans infect ...201526371125
validation and clinical application of a molecular method for the identification of cryptococcus neoformans/cryptococcus gattii complex dna in human clinical specimens.the diagnosis of cryptococcosis is usually performed based on cultures of tissue or body fluids and isolation of the fungus, but this method may require several days. direct microscopic examination, although rapid, is relatively insensitive. biochemical and immunodiagnostic rapid tests are also used. however, all of these methods have limitations that may hinder final diagnosis. the increasing incidence of fungal infections has focused attention on tools for rapid and accurate diagnosis using mo ...201526365230
characterization of the virulence of cryptococcus neoformans strains in an insect model. 201526364757
usefulness of intraventricular infusion of antifungal drugs through ommaya reservoirs for cryptococcal meningitis treatment.cryptococcal meningitis is a severe infection among immunosuppressed individuals, with a high mortality rate. although amphotericin b is the first-choice drug for treatment, its use is restricted when adverse effects are clinically problematic. the usefulness of intraventricular infusion of antifungal drugs through ommaya reservoirs for cryptococcal meningitis treatment has been unconfirmed. we evaluated the efficacy of intraventricular infusion of amphotericin b through ommaya reservoirs.201526362338
inhibitory activity of isoniazid and ethionamide against cryptococcus biofilms.in recent years, the search for drugs to treat systemic and opportunistic mycoses has attracted great interest from the scientific community. this study evaluated the in vitro inhibitory effect of the antituberculosis drugs isoniazid and ethionamide alone and combined with itraconazole and fluconazole against biofilms of cryptococcus neoformans and cryptococcus gattii. antimicrobials were tested at defined concentrations after susceptibility assays with cryptococcus planktonic cells. in addition ...201526362025
genome-wide transcription study of cryptococcus neoformans h99 clinical strain versus environmental strains.the infection of cryptococcus neoformans is acquired through the inhalation of desiccated yeast cells and basidiospores originated from the environment, particularly from bird's droppings and decaying wood. three environmental strains of c. neoformans originated from bird droppings (h4, s48b and s68b) and c. neoformans reference clinical strain (h99) were used for intranasal infection in c57bl/6 mice. we showed that the h99 strain demonstrated higher virulence compared to h4, s48b and s68b strai ...201526360021
stat1 signaling within macrophages is required for antifungal activity against cryptococcus neoformans.cryptococcus neoformans, the predominant etiological agent of cryptococcosis, is an opportunistic fungal pathogen that primarily affects aids patients and patients undergoing immunosuppressive therapy. in immunocompromised individuals, c. neoformans can lead to life-threatening meningoencephalitis. studies using a virulent strain of c. neoformans engineered to produce gamma interferon (ifn-γ), denoted h99γ, demonstrated that protection against pulmonary c. neoformans infection is associated with ...201526351277
cryptococcosis due to cryptococcus gattii in germany from 2004-2013.the fungal pathogen cryptococcus gattii was considered to be restricted to tropic and sub- tropic regions. a recent outbreak in north america due to isolates belonging to molecular type vg ii, affecting mostly non-immunocompromised hosts, documented the potential public health impact of this fungal pathogen also in temperate regions. surveillance of these infections in germany is challenging, as cryptococcosis is not notifiable and often c. gattii is diagnostically not distinguished from the mor ...201526341329
pitfalls in serological diagnosis of cryptococcus gattii infections.the detection of cryptococcal antigen by latex agglutination tests (lats), enzyme-linked immunoassays (elisa), or lateral flow assay (lfa) is an important tool for diagnosis of a cryptococcus infection. cerebrospinal fluid and/or serum samples of 10 patients with cryptococcosis due to cryptococcus gattii or a hybrid of cryptococcus neoformans and c. gattii were examined by three lats (the immy latex-crypto(®) test, the pastorex(tm) crypto plus, and the remel cryptococcus antigen test kit) and th ...201526337090
in vitro interaction of antifungal and antibacterial drugs against cryptococcus neoformans var. grubii before and after capsular induction.this study evaluated the synergistic interactions between amphotericin b (amb) and azithromycin (azm), daptomycin (dap), linezolid (lnz), minocycline (mino), fluconazole (flz), flucytosine (5fc), linezolid (lzd), or tigecycline (tig) against clinical isolates of cryptococcus neoformans var. grubii before and after capsule induction. high synergism (>75%) was observed for the combinations, amb+5fc, amb+tig, amb+azm, amb+lzd and amb+mino but only in the strains after capsule induction. the results ...201526333356
cryptococcus neoformans infection and immune cell regulation in human monocytes.cryptococcus neoformans infections are becoming increasingly prevalent and remain a life-threatening clinical issue in immune-compromised hosts. the microorganism evades a variety of endogenous anti-fungal mechanims of host immune cells. the signaling pathways in human immune cells that become activated in response to cryptococcus neoformans infection have yet to be fully characterized.201526328591
increased antifungal drug resistance in clinical isolates of cryptococcus neoformans in uganda.cryptococcal antigen screening is recommended among people living with aids when entering hiv care with a cd4 count of <100 cells/μl, and preemptive fluconazole monotherapy treatment is recommended for those with subclinical cryptococcal antigenemia. yet, knowledge is limited of current antimicrobial resistance in africa. we examined antifungal drug susceptibility in 198 clinical isolates collected from kampala, uganda, between 2010 and 2014 using the clsi broth microdilution assay. in compariso ...201526324276
role of sterylglucosidase 1 (sgl1) on the pathogenicity of cryptococcus neoformans: potential applications for vaccine development.cryptococcosis caused by cryptococcus neoformans and cryptococcus gattii affects a large population and is a cause of significant morbidity and mortality. despite its public health burden, there are currently no vaccines against cryptococcosis and new strategies against such infections are needed. in this study, we demonstrate that c. neoformans has the biochemical ability to metabolize sterylglucosides (sgs), a class of immunomodulatory glycolipids. genetic manipulations that eliminate cryptoco ...201526322039
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