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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
secondary mania due to aids and cryptococcal meningitis in a 78-year-old patient.we report a 78-year-old man without past psychiatric history who experienced his first manic episode successfully treated with quetiapine and lorazepam, but was ultimately found to have aids and cryptococcus neoformans meningitis. our presented case highlights the importance of comprehensive differential diagnoses to rule out secondary causes of psychiatric symptoms presenting for the first time in elderly patients.201625919146
[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
neuromeningeal cryptococcosis in sub-saharan africa: killer disease with sparse data.the extent of neuromeningeal cryptococcosis (nmc) has increased since the advent of hiv/aids. it has non-specific clinical signs but marked by high mortality.201725883484
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
the effects of the f-actin inhibitor latrunculin a on the pathogenic yeast cryptococcus neoformans.this basic research aimed to investigate the effects of the actin inhibitor latrunculin a (la) on the human pathogen cryptococcus neoformans, by freeze-substitution (fs) and electron microscopy (em), to determine whether the actin cytoskeleton can become a new antifungal target for inhibition of cell division.201425823986
synthesis and biological evaluation of novel 3-substituted amino-4-hydroxylcoumarin derivatives as chitin synthase inhibitors and antifungal agents.a series of novel 3-substituted amino-4-hydroxycoumarin derivatives have been designed and synthesized as chitin synthase (chs) inhibitors. all the synthesized compounds have been screened for their chs inhibition activity and antimicrobial activity in vitro. the enzymatic assay indicated that most of the compounds have good inhibitory activity against chs, in which compound 6o with ic50 of 0.10 mmol/l had stronger activity than that of polyoxins b, which acts as control drug with ic50 of 0.18 m ...201625815669
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
an enabling act.infection with human t-lymphotropic virus type 1 (htlv-1) can be associated with hematologic malignancy, inflammatory syndromes, or infectious complications. herein, we bring attention to htlv-1 infection complications as we discuss a case of disseminated cryptococcosis in a patient with htlv-1-associated t cell lymphoma.201425734082
characterization of lipids and proteins associated to the cell wall of the acapsular mutant cryptococcus neoformans cap 67.cryptococcus neoformans is an opportunistic human pathogen that causes life-threatening meningitis. in this fungus, the cell wall is exceptionally not the outermost structure due to the presence of a surrounding polysaccharide capsule, which has been highly studied. considering that there is little information about c. neoformans cell wall composition, we aimed at describing proteins and lipids extractable from this organelle, using as model the acapsular mutant c. neoformans cap 67. purified ce ...201725733123
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
effects of microtubule and actin inhibitors on cryptococcus neoformans examined by scanning and transmission electron microscopy.cryptococcus neoformans is one of the most important human fungal pathogens. its cells contain rich microtubules required for nuclear division and rich f-actin cytoskeletons for cell division. disruption of microtubules by a microtubule inhibitor should block nuclear division, and disruption of f-actin by an actin inhibitor should block cell division. we investigated the effects of microtubule and actin inhibitors to find out whether the cytoskeletons of c. neoformans can become a new anti-funga ...201425720843
endophytic fungal compounds active against cryptococcus neoformans and c. gattii.infections with cryptococcus are invasive mycoses associated with significant morbidity and mortality, mainly in immunosuppressed patients. several drugs have been introduced to combat these opportunistic infections. however, resistance of this organism to antifungal drugs has increased, causing difficulties in the treatment. the goal of this work was to evaluate the antifungal activity of ethanol extracts from endophytic fungi isolated from plants collected from different brazilian ecosystems a ...201525712396
cryptococcal meningitis in chinese patients with systemic lupus erythematosus.systemic lupus erythematosus (sle) is a chronic immunologic disorder that can affect multiple organ systems and makes the patient susceptible to infection. cryptococcal meningitis (cm) is a rare but often fatal complication of sle.201525704191
primary laryngeal cryptococcosis resembling laryngeal carcinoma.a case of an 82-year-old female with primary laryngeal cryptococcosis who had undergone long-term corticosteroid therapy for chronic obstructive pulmonary disease and rheumatoid arthritis is reported. she complained hoarseness with swallowing pain and irritability of the larynx for over a month. endoscopic examination revealed a white, exudative irregular region on right arytenoid that mimicked a laryngeal carcinoma. histological examination showed pseudoepitheliomatous hyperplasia and severe su ...201525701260
comparison of different in vitro tests to detect cryptococcus neoformans not susceptible to amphotericin b.infections due to cryptococcus neoformans cause severe disease, mostly in aids patients. the antifungal drug recommended for the initial treatment of these infections is amphotericin b with or without flucytosine, but treatment failure occurs, associated with high mortality. thus, antifungal susceptibility testing is needed. however, the in vitro susceptibility tests available for c. neoformans are not useful to detect isolates that are not susceptible to antifungal agents such as amphotericin b ...201525700663
neuroimaging of hiv-associated cryptococcal meningitis: comparison of magnetic resonance imaging findings in patients with and without immune reconstitution.to determine the frequency, imaging characteristics, neuroanatomical distribution and dynamics of magnetic resonance imaging findings in hiv-associated cryptococcal meningitis in immunocompromised patients we compared patients without antiretroviral therapy with patients undergoing immune reconstitution. neuroimaging and clinical data of 21 consecutive patients presenting to a german hiv centre in a 10-year period between 2005 and 2014 were reviewed. we identified eight patients with magnetic re ...201625693580
a rare case of cryptococcus gattii pneumonia in a renal transplant patient.cryptococcus neoformans and cryptococcus gattii are environmental fungi that can cause fever, cough, pneumonia, meningoencephalitis, dissemination, and death. c. gattii causes cryptococcomas more frequently than does c. neoformans and may require prolonged antifungal treatment. we present a rare case of c. gattii pneumonia in a renal transplant patient. a 44-year-old man, living in a rural area endemic for c. gattii and who had received a kidney transplant, was admitted to the hospital with feve ...201525689604
aging: an emergent phenotypic trait that contributes to the virulence of cryptococcus neoformans.the pathogenic fungus, cryptococcus neoformans, is known to undergo phenotypic variation, which affects its virulence in the host. recent investigations on c. neoformans cells in humans have validated the concept that phenotypic variation is present and relevant for the outcome of chronic cryptococcosis. the c. neoformans capsule is not the only trait that varies among strains. an emerging variant is the "old cell phenotype" generated when c. neoformans undergoes replicative aging. this phenotyp ...201525689531
positional cloning in cryptococcus neoformans and its application for identification and cloning of the gene encoding methylenetetrahydrofolate reductase.cryptococcus neoformans, a basidiomycetous human pathogenic yeast, has been widely used in research fields in medical mycology as well as basic biology. gene cloning or identification of the gene responsible for a mutation of interest is a key step for functional analysis of a particular gene. the availability therefore, of the multiple methods for cloning is desirable. in this study, we proposed a method for a mapping-based gene identification/cloning (positional cloning) method in c. neoforman ...201525687932
puf4 regulates both splicing and decay of hxl1 mrna encoding the unfolded protein response transcription factor in cryptococcus neoformans.the endoplasmic reticulum (er) responds to errors in protein folding or processing by induction of the unfolded protein response (upr). during conditions of er stress, unconventional splicing of an mrna encoding the upr-responsive transcription factor occurs at the er surface, resulting in activation of the upr. upr activation is necessary for adaptation to er stress and for the pathogenic fungus cryptococcus neoformans is an absolute requirement for temperature adaptation and virulence. in this ...201525681267
cryptococcus gattii urease as a virulence factor and the relevance of enzymatic activity in cryptococcosis pathogenesis.ureases (ec 3.5.1.5) are ni(2+) -dependent metalloenzymes produced by plants, fungi and bacteria that hydrolyze urea to produce ammonia and co2 . the insertion of nickel atoms into the apo-urease is better characterized in bacteria, and requires at least three accessory proteins: ured, uref, and ureg. our group has demonstrated that ureases possess ureolytic activity-independent biological properties that could contribute to the pathogenicity of urease-producing microorganisms. the presence of u ...201525675897
cryptococcal brainstem abscess mimicking brain tumors in an immunocompetent patient.usually fungal infections caused by opportunistic and pathogenic fungi had been an important cause of morbidity and mortality among immunocompromised patients. however clinical data and investigations for immunocompetent pathogenic fungal infections had been rare and neglected into clinical studies. especially cryptococcal brainstem abscess cases mimicking brain tumors were also much more rare. so we report this unusual case. this 47-year-old man presented with a history of progressively worseni ...201525674344
cryptococcus gattii sero-mating type allelic pattern determined by multiplex pcr.molecular methods to differentiate serotypes, mating types and molecular types of cryptococcus neoformans and c. gattii are important tools to understand epidemiology and pathogenesis of these pathogens. in this study, a multiplex polymerase chain reaction (pcr) approach was applied to sero-mating typing of c. gattii strains. four pairs of primers were designed to target 4 allele-specific genes located in the mating-type locus. twenty-three c. gattii strains, presenting different mating types an ...201525658561
fatal cryptococcosis involving multiple sites in an immunocompetent child.disseminated cryptococcosis is less common in immunocompetent individuals. herein, we report a fatal case of cryptococcosis in apparently immunocompetent child with multiple site involvement. the yeast isolated from cerebrospinal fluid, blood, endotracheal, gastric and lymph node aspirate was identified by molecular method as cryptococcus neoformans var. grubii.201525657136
massive cerebral edema resulting in brain death as a complication of cryptococcus neoformans meningitis.despite the widespread use of highly active antiretroviral therapy, cryptococcal meningoencephalitis has emerged as the second leading cause of infectious morbidity and mortality in hiv-infected patients worldwide. it presents usually as subacute or chronic disease but occasionally may be fulminant. common clinical presentations included headache, fever, and depressed level of consciousness. the infection affects both the subarachnoid space and brain parenchyma, and is characterized by a paucity ...201525656669
uniparental mitochondrial dna inheritance is not affected in ustilago maydis δatg11 mutants blocked in mitophagy.maternal or uniparental inheritance (upi) of mitochondria is generally observed in sexual eukaryotes, however, the underlying mechanisms are diverse and largely unknown. recently, based on the use of mutants blocked in autophagy, it has been demonstrated that autophagy is required for strict maternal inheritance in the nematode caenorhabditis elegans. uniparental mitochondrial dna (mtdna) inheritance has been well documented for numerous fungal species, and in particular, has been shown to be ge ...201525652096
macrophage mitochondrial and stress response to ingestion of cryptococcus neoformans.human infection with cryptococcus neoformans, a common fungal pathogen, follows deposition of yeast spores in the lung alveoli. the subsequent host-pathogen interaction can result in eradication, latency, or extrapulmonary dissemination. successful control of c. neoformans infection is dependent on host macrophages, but macrophages display little ability to kill c. neoformans in vitro. recently, we reported that ingestion of c. neoformans by mouse macrophages induces early cell cycle progression ...201525646306
skeletal cryptococcosis from 1977 to 2013.skeletal cryptococcosis, an aspect of disseminated cryptococcal disease or isolated skeletal cryptococcal infection, is a rare but treatable disease. however, limited information is available regarding its clinical features, treatment, and prognosis. this systematic review examined all cases published between april 1977 and may 2013 with regard to the factors associated with this disease, including patient sex, age, and epidemiological history; affected sites; clinical symptoms; underlying disea ...201425642211
a flow cytometry method for testing the susceptibility of cryptococcus spp. to amphotericin b.human fungal infections have increased at an alarming rate in recent years, particularly in immunocompromised individuals. cryptococcosis is the second most prevalent systemic fungal infection worldwide, and the most prevalent systemic infection in immunocompromised individuals, representing more than 70% of cases. the incidence of cryptococcosis is high in people with hiv/acquired immunodeficiency syndrome (aids), with recent estimates indicating that there are one million cases of cryptococcal ...201525639695
antibiotic-producing bacteria from stag beetle mycangia.the search for new antibiotics or antifungal agents is crucial for the chemotherapies of infectious diseases. the limited resource of soil bacteria makes it difficult to discover such new drug candidate. we, therefore, focused on another bacterial resource than soil bacteria, the microbial flora of insect species. in the present study, we isolated 40 strains of bacteria and fungi from the mycangia of three species of stag beetle, dorcus hopei binodulosus, dorcus rectus, and dorcus titanus pilife ...201525639488
[genotypes and epidemiology of clinical isolates of cryptococcus neoformans in corrientes, argentina]. 201525638353
response to therapy in patients with cryptococcosis and aids: association with in vitro susceptibility to fluconazole.the implications of the cryptococcus neoformans resistance to fluconazole on patient therapy have not been fully elucidated due to the discordant results found in published studies.201525637338
cryptococcus neoformans-induced macrophage lysosome damage crucially contributes to fungal virulence.upon ingestion by macrophages, cryptococcus neoformans can survive and replicate intracellularly unless the macrophages become classically activated. the mechanism enabling intracellular replication is not fully understood; neither are the mechanisms that allow classical activation to counteract replication. c. neoformans-induced lysosome damage was observed in infected murine bone marrow-derived macrophages, increased with time, and required yeast viability. to demonstrate lysosome damage in th ...201525637026
latex agglutination: diagnose the early cryptococcus neoformans test of capsular polysaccharide antigen.this paper aims to discuss the early diagnosis value of latex agglutination test in cryptococcal meningitis. the cerebrospinal fluid (csf) of 112 patients with definite cryptococcal meningitis and 26 patients with tubercular meningitis and virus meningitis were collected, latex agglutination test is adopted to detect cryptococcal capsular polysaccharide antigen. then it was compared with fungal culture and direct microscopy method for evaluating the sensitivity and specificity of the diagnosis. ...201525631497
identification and properties of plasma membrane azole efflux pumps from the pathogenic fungi cryptococcus gattii and cryptococcus neoformans.cryptococcus gattii from the north american northwest (nw) have higher azole mics than do non-nw c. gattii or cryptococcus neoformans. since mechanisms of azole resistance in c. gattii are not known, we identified c. gattii and c. neoformans plasma membrane azole efflux pumps and characterized their properties.201525630649
duodenal cryptococcus infection in an aids patient: retrospective clinical analysis.cryptococcal infection primarily affects the lung or the central nervous system and rare cases have been reported involving the gastrointestinal tract. however, among patients with hiv/aids, the gastrointestinal involvement is increasing. according to the pubmed search results, there were seven cases reported involving duodenal cryptococcosis combined with aids in five reports. here, we report the case of a patient found to have aids combined with duodenal, pulmonary, and subsequent neurological ...201525629567
rapid microscopy and use of vital dyes: potential to determine viability of cryptococcus neoformans in the clinical laboratory.cryptococcus neoformans is the commonest cause of fungal meningitis, with a substantial mortality despite appropriate therapy. quantitative culture of cryptococci in cerebrospinal fluid (csf) during antifungal therapy is of prognostic value and has therapeutic implications, but is slow and not practicable in many resource-poor countries.201525625210
next generation multilocus sequence typing (ngmlst) and the analytical software program mlstez enable efficient, cost-effective, high-throughput, multilocus sequencing typing.multilocus sequence typing (mlst) has become the preferred method for genotyping many biological species, and it is especially useful for analyzing haploid eukaryotes. mlst is rigorous, reproducible, and informative, and mlst genotyping has been shown to identify major phylogenetic clades, molecular groups, or subpopulations of a species, as well as individual strains or clones. mlst molecular types often correlate with important phenotypes. conventional mlst involves the extraction of genomic d ...201525624069
capsular polysaccharides from cryptococcus neoformans modulate production of neutrophil extracellular traps (nets) by human neutrophils.in the present study, we characterized the in vitro modulation of nets (neutrophil extracellular traps) induced in human neutrophils by the opportunistic fungus cryptococcus neoformans, evaluating the participation of capsular polysaccharides glucuronoxylomanan (gxm) and glucuronoxylomannogalactan (gxmgal) in this phenomenon. the mutant acapsular strain cap67 and the capsular polysaccharide gxmgal induced net production. in contrast, the wild-type strain and the major polysaccharide gxm did not ...201525620354
postpartum cryptococcal pulmonary lesion incidentally discovered during a pulmonary-embolism evaluation of a 28-year-old caucasian woman.we report a case of localized pulmonary cryptococcal infection in a 28-year-old caucasian woman who was 1 month postpartum at the time of her arrival at the hospital. the patient reported right-side chest pain; on further work up, she was found to have an incidental pulmonary lesion of the left lower lung lobe. surgical pathology examination and microbiology studies revealed localized cryptococcal infection. cases of cryptococcal pneumonia in pregnant women and in the postpartum period have been ...201525617397
cryptococcal phospholipase b1 is required for intracellular proliferation and control of titan cell morphology during macrophage infection.cryptococcus neoformans is an opportunistic fungal pathogen and a leading cause of fungal-infection-related fatalities, especially in immunocompromised hosts. several virulence factors are known to play a major role in the pathogenesis of cryptococcal infections, including the enzyme phospholipase b1 (plb1). compared to other well-studied cryptococcus neoformans virulence factors such as the polysaccharide capsule and melanin production, very little is known about the contribution of plb1 to cry ...201525605772
application of the diversilab system for tracing the source of the mixed infections caused by cryptococcus neoformans var. grubii from a patient with systemic lupus erythematosus.two strains of cryptococcus neoformans (pu 66 and pu112) were simultaneously isolated from a patient with systemic lupus erythematosus. we aimed to trace the source of the mixed infections. multi-locus sequence typing (mlst) and the diversilab system analyses were performed on the 2 clinical and 23 environmental c. neoformans from pigeon droppings, 11 from the home (h1) the patient visited, 12 from another home (h2) as control. all the strains were uniformly genotyped as c. neoformans var. grubi ...201525591136
utility of bone marrow examination for workup of fever of unknown origin in patients with hiv/aids.the utility of bone marrow aspiration and biopsy (bmab) as a diagnostic tool in patients with hiv/aids and fever of unknown origin (fuo) is a subject of debate. because highly active antiretroviral therapy has reduced incidence of opportunistic infections, it is important to reassess the efficacy of bmab for this diagnostic purpose. to our knowledge, no such studies have been performed in harris county which has the highest incidence of hiv in the state of texas.201525589792
distribution of yeast isolates from invasive infections and their in vitro susceptibility to antifungal agents: evidence from 299 cases in a 3-year (2010 to 2012) surveillance study.invasive yeast infections cause significant morbidity and mortality. surveillance for the infection is necessary to detect trends in species distribution and antifungal resistance. we performed this retrospective study of yeast infection at jinling hospital, nanjing in china, from year of 2010 to 2012. a total of 341 yeast isolates were obtained from patients with invasive infections in the period. among these isolates, candida spp. comprised of the highest percentage of yeast strains (91.8 %), ...201525588889
mitochondrial dna inheritance in the human fungal pathogen cryptococcus gattii.the inheritance of mitochondrial dna (mtdna) is predominantly uniparental in most sexual eukaryotes. in this study, we examined the mitochondrial inheritance pattern of cryptococcus gattii, a basidiomycetous yeast responsible for the recent and ongoing outbreak of cryptococcal infections in the us pacific northwest and british columbia (especially vancouver island) in canada. using molecular markers, we analyzed the inheritance of mtdna in 14 crosses between strains within and between divergent ...201525577978
antifungal activity of the essential oil of angelica major against candida, cryptococcus, aspergillus and dermatophyte species.the composition and antifungal activity of the essential oil (eo) of angelica major and its main components α-pinene and cis-β-ocimene against clinically relevant yeasts and moulds were evaluated. eo from the plant's aerial parts was obtained by hydrodistillation and analysed by gas chromatography (gc) and gas chromatography/mass spectrometry (gc/ms). the oil showed high contents of α-pinene (21.8 %) and cis-β-ocimene (30.4 %). minimum inhibitory concentrations (mics) were measured according to ...201525576097
primary cutaneous cryptococcosis in an eight-year-old immunocompetent child: how to treat?here we report on a case of primary cryptococcal skin infection in an immunocompetent 8-year-old boy. the infection first manifested itself as a subcutaneous abscess around the proximal joint of his right thumb after a minor injury from contact with a thorny shrub. after surgical incision and drainage was performed, cryptococcus neoformans var. neoformans was the only pathogen cultured from the lesion. an agglutination test for the capsular antigen in serum displayed negative results and the imm ...201525565197
a case of miliary pulmonary cryptococcosis and review of literature.we describe a case of cryptococcal fungemia in a 62-year-old male renal transplant patient. the diagnosis was established by isolation of cryptococcus neoformans using the isolator(®) blood culture lysis-centrifugation system. testing for cryptococcal antigens was negative in the serum and cerebrospinal fluid. transbronchial lung biopsies and bronchoalveolar lavage were negative. antifungal therapy with fluconazole was started, resulting in fever remission, and a sustained clinical response was ...201525563716
molecular characterization and antifungal susceptibility of cryptococcus neoformans strains collected from a single institution in lima, peru.cryptococcosis is a fungal infection with a worldwide distribution, mainly caused by cryptococcus neoformans and cryptococcus gattii.201525556051
leu1 plays a role in iron metabolism and is required for virulence in cryptococcus neoformans.amino acid biosynthetic pathways that are absent in mammals are considered an attractive target for antifungal therapy. leucine biosynthesis is one such target pathway, consisting of a five-step conversion process starting from the valine precursor 2-keto-isovalerate. isopropylmalate dehydrogenase (leu1) is an fe-s cluster protein that is required for leucine biosynthesis in the model fungus saccharomyces cerevisiae. the human pathogenic fungus cryptococcus neoformans possesses an ortholog of s. ...201525554701
is cryptococcus gattii a primary pathogen?the two etiologic agents of cryptococcal meningoencephalitis, cryptococcus neoformans and c. gattii, have been commonly designated as either an opportunistic pathogen for the first species or as a primary pathogen for the second species. such a distinction has been based on epidemiological findings that the majority of patients presenting meningoencephalitis caused by c. neoformans are immunocompromised while c. gattii infection has been reported more often in immunocompetent patients. a recent ...201527795955
first description of oral cryptococcus neoformans causing osteomyelitis of the mandible, manubrium and third rib with associated soft tissue abscesses in an immunocompetent host.the majority of disseminated cryptococcal infections occur in patients with acquired immunodeficiency syndrome (aids), with only 11-14% of cases occurring in patients without aids. most non-aids related cases (75%) occur in patients with another immune deficiency. here, we present the first case of mucocutaneous cryptococcal disease in an immunocompetent host, review the epidemiology of risk factors associated with disseminated cryptococcal disease, and describe a rational workup for a possible ...201727227123
etiological factors of cryptococcosis - what makes them pathogens ?a significant participation in the growing prevalence of fungal infections have basidiomycete yeasts of the genus of cryptococcus. among about seventy actually known species belonging to cryptococcus genus there are only two: cryptococcus neoformans and cryptococcus gattii, which as anamorphs in parasitic stage of its life fully evolved the mechanisms predisposing them to be a human and animal pathogens. specific attributes important in the pathogenesis of cryptococcosis called virulence factors ...201527019916
macrophage cholesterol depletion and its effect on the phagocytosis of cryptococcus neoformans.cryptococcosis is a life-threatening infection caused by pathogenic fungi of the genus cryptococcus. infection occurs upon inhalation of spores, which are able to replicate in the deep lung. phagocytosis of cryptococcus by macrophages is one of the ways that the disease is able to spread into the central nervous system to cause lethal meningoencephalitis. therefore, study of the association between cryptococcus and macrophages is important to understanding the progression of the infection. the p ...201425549203
design, synthesis, and biological evaluation of aminothiazole derivatives against the fungal pathogens histoplasma capsulatum and cryptococcus neoformans.invasive fungal disease constitutes a growing health burden and development of novel antifungal drugs with high potency and selectivity against new fungal molecular targets are urgently needed. previously, an aminothiazole derivative, designated as 41f5, was identified in our laboratories as highly active against histoplasma yeast (mic50 0.4-0.8 μm) through phenotypic high-throughput screening of a commercial library of 3600 purine mimicking compounds (antimicrob. agents chemother.2013, 57, 4349 ...201525543205
generation of stable mutants and targeted gene deletion strains in cryptococcus neoformans through electroporation.cryptococcus neoformans is the etiologic agent of cryptococcal meningitis that causes more than half a million deaths worldwide each year. this capsulated basidiomycetous yeast also serves as a model for micropathogenic studies. the ability to make stable mutants, either via ectopic integration or homologous recombination, has been accomplished using biolistic transformation. this technical advance has greatly facilitated the research on the basic biology and pathogenic mechanisms of this pathog ...201525541555
antifungal amphiphilic aminoglycoside k20: bioactivities and mechanism of action.k20 is a novel amphiphilic antifungal aminoglycoside that is synthetically derived from the antibiotic kanamycin a. reported here are investigations of k20's antimicrobial activities, cytotoxicity, and fungicidal mechanism of action. in vitro growth inhibitory activities against a variety of human and plant pathogenic yeasts, filamentous fungi, and bacteria were determined using microbroth dilution assays and time-kill curve analyses, and hemolytic and animal cell cytotoxic activities were deter ...201425538692
product binding enforces the genomic specificity of a yeast polycomb repressive complex.we characterize the polycomb system that assembles repressive subtelomeric domains of h3k27 methylation (h3k27me) in the yeast cryptococcus neoformans. purification of this prc2-like protein complex reveals orthologs of animal prc2 components as well as a chromodomain-containing subunit, ccc1, which recognizes h3k27me. whereas removal of either the ezh or eed ortholog eliminates h3k27me, disruption of mark recognition by ccc1 causes h3k27me to redistribute. strikingly, the resulting pattern of h ...201525533783
cryptococcus neoformans induces antimicrobial responses and behaves as a facultative intracellular pathogen in the non mammalian model galleria mellonella.cryptococcus neoformans is an encapsulated opportunistic fungal pathogen that is found in multiple niches in the environment and that can cause fatal meningoencephalitis in susceptible patients, mainly hiv+ individuals. cryptococcus also infects environmental hosts such as nematodes, insects and plants. in particular, c. neoformans can kill the lepidopteran galleria mellonella, which offers a useful tool to study microbial virulence and drug efficacy. galleria mellonella immunity relies on innat ...201525531532
cryptococcosis in patients living with hepatitis c and b viruses.cryptococcosis, a systemic fungal infection, has become a significant, global public health problem. patients with liver disease have an increased predisposition to infections, such as cryptococcosis. to report the underlying disease, the variety of etiologic agents involved and the outcomes of the cryptococcosis in patients living with hbv and/or hcv, we reviewed 34 medical records of patients who were diagnosed with cryptococcosis by the mycology laboratory of santa casa hospital, porto alegre ...201525528539
cryptococcus neoformans prosthetic joint infection: case report and review of the literature.a 77-year-old woman with diabetes mellitus, myasthenia gravis and bilateral total hip arthroplasties underwent a two-stage procedure followed by treatment with vancomycin for a coagulase-negative staphylococcal prosthetic hip infection. this was complicated by a spontaneous left hip dislocation with a hematoma that was evacuated; all intraoperative cultures grew out cryptococcus neoformans. treatment with intravenous liposomal amphotericin b was started. her prosthetic device was retained, and s ...201525524725
molecular diagnosis of cryptococcal meningitis in cerebrospinal fluid: comparison of primer sets for cryptococcus neoformans and cryptococcus gattii species complex.this study evaluated the use of polymerase chain reaction for cryptococcal meningitis diagnosis in clinical samples.201525523072
toward improved anti-cryptococcal drugs: novel molecules and repurposed drugs.cryptococcosis is one of the most important fungal infections of humans. it primarily, but not exclusively, afflicts people with compromised immune function. cryptococcosis is most commonly caused by cryptococcus neoformans var. grubii with c. neoformans var. neoformans and c. gatti also contributing to the disease. cryptococcosis is primarily manifested as meningoencephalitis although pneumonia occurs frequently as well. globally, the burden of disease is highest among those living with hiv/aid ...201525514636
cryptococcal meningoencephalitis relapse after an eight-year delay: an interplay of infection and immune reconstitution.we report a case of a symptomatic relapse of hiv-related cryptococcal meningoencephalitis eight years after the first diagnosis on the background of immune reconstitution. the findings as well as the clinical course suggests a combination of smouldering localised infection and enhanced inflammatory reaction related to immune restoration due to antiretroviral therapy. a combination of antifungal and anti-inflammatory therapy resulted in clinical and radiological improvement. our case challenges t ...201525505049
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