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a major role for capsule-independent phagocytosis-inhibitory mechanisms in mammalian infection by cryptococcus neoformans.the antiphagocytic polysaccharide capsule of the human fungal pathogen cryptococcus neoformans is a major virulence attribute. however, previous studies of the pleiotropic virulence determinant gat201, a gata family transcription factor, suggested that capsule-independent antiphagocytic mechanisms exist. we have determined that gat201 controls the mrna levels of ~1100 genes (16% of the genome) and binds the upstream regions of ~130 genes. seven gat201-bound genes encode for putative and known tr ...201121402362
optimization of 3-(phenylthio)quinolinium compounds against opportunistic fungal pathogens.ring-opened benzothieno[3,2-b]quinolinium salts (3) were designed and synthesized with substitution on the thiophene moiety. in vitro screenings were carried out against fungal pathogens including cryptococcus neoformans, candida albicans, candida glabrata, candida krusei and aspergillus fumigatus. in all, by replacing the n-methyl group (2) with n-?-phenylpentyl or ?-cyclohexylpentyl group to form substituted 3-(phenylthio)quinolinium compounds produced remarkable potencies, as high as 300-fold ...201121402432
carbonic anhydrase inhibitors. inhibition of the ß-class enzymes from the fungal pathogens candida albicans and cryptococcus neoformans with branched aliphatic/aromatic carboxylates and their derivatives.the inhibition of the ß-carbonic anhydrases (cas, ec 4.2.1.1) from the pathogenic fungi cryptococcus neoformans (can2) and candida albicans (nce103) with a series of 25 branched aliphatic and aromatic carboxylates has been investigated. human isoforms hca i and ii were also included in the study for comparison. aliphatic carboxylates were generally millimolar hca i and ii inhibitors and low micromolar/submicromolar ß-ca inhibitors. aromatic carboxylates were micromolar inhibitors of the four enz ...201121402476
design, synthesis and antifungal activities of novel 1,2,4-triazole derivatives.a series of novel 1,2,4-triazole derivatives with a 4-(4-substitutedphenyl) piperazine side chain were designed and synthesized based on the structure of lanosterol 14a-demethylase (cyp51). their antifungal activities against eight human pathogenic fungi were evaluated in vitro by measuring the minimal inhibitory concentrations. nearly all tested compounds were found to be more potent against candida albicans than control drug fluconazole. noticeably, the mic(80) value of compounds 6,7,9,14 and ...201121420761
[effect of hiv-1gp41 ectodomain on cryptococcus neoformans-induced cytoskeletal changes in human brain microvascular endothelial cells].to study the effect of hiv-1 gp41 ectodomain (gp41-i90) on the cytoskeletal changes in human brain microvascular endothelial cells (hbmecs) induced by cryptococcus neoformans.201121421487
cryptococcosis presenting as anterior neck swelling in an immunocompetent man: a case report.cryptococcosis is caused by the encapsulated opportunistic yeast cryptococcus neoformans. an immunocompromised host is more susceptible to the survival and dissemination of this yeast, which can occur to almost all organs of the body, especially the central nervous system, lungs, bone marrow, gastrointestinal tract, retina, and reticuloendothelial system. however, there are few reports of cryptococcus causing infections ir immunocompetent hosts.201021428161
nitrogen metabolite repression of metabolism and virulence in the human fungal pathogen cryptococcus neoformans.proper regulation of metabolism is essential to maximizing fitness of organisms in their chosen environmental niche. nitrogen metabolite repression is an example of a regulatory mechanism in fungi that enables preferential utilization of easily assimilated nitrogen sources, such as ammonium, to conserve resources. here we provide genetic, transcriptional, and phenotypic evidence of nitrogen metabolite repression in the human pathogen cryptococcus neoformans. in addition to loss of transcriptiona ...201121441208
[photo quiz: basic mycology]. 201121441706
[phosphate regulation in cryptococcus neoformans]. 201121441709
trends in antifungal drug susceptibility of cryptococcus neoformans isolates obtained through population-based surveillance in south africa in 2002-2003 and 2007-2008.cryptococcus neoformans is the most common cause of meningitis among adult south africans with hiv infection/aids. widespread use of fluconazole for treatment of cryptococcal meningitis and other hiv-associated opportunistic fungal infections in south africa may lead to the emergence of isolates with reduced fluconazole susceptibility. mic testing using a reference broth microdilution method was used to determine if isolates with reduced susceptibility to fluconazole or amphotericin b had emerge ...201121444707
protective immunity against experimental pulmonary cryptococcosis in t cell-depleted mice.individuals with defects in t cell-mediated immunity (cmi) are highly susceptible to infection with cryptococcus neoformans. the purpose of these studies was to determine if protection against experimental pulmonary cryptococcosis can be generated in t cell-deficient hosts. balb/c mice were depleted of cd4?and/or cd8? t cells or given an isotype control antibody prior to vaccination with a c. neoformans strain, designated h99?, previously shown to induce protection against c. neoformans infectio ...201121450975
sec14 is a specific requirement for secretion of phospholipase b1 and pathogenicity of cryptococcus neoformans.secreted phospholipase b1 (cnplb1) is essential for dissemination of cryptococcus neoformans to the central nervous system (cns) yet essential components of its secretion machinery remain to be elucidated. using gene deletion analysis we demonstrate that cnplb1 secretion is dependent on the cnsec14 product, cnsec14-1p. cnsec14-1p is a homologue of the phosphatidylinositol transfer protein scsec14p, which is essential for secretion and viability in saccharomyces cerevisiae. in contrast to cnplb1, ...201121453402
cryptococcal pneumonia in a hiv positive patient: a pre- and post-mortem view. 201121456379
concurrent cryptococcal and pneumocystis pneumonia along with pulmonary tuberculosis in an hiv-positive patient: lessons learned for early management.case: we are presenting a 50-year-old patient of pulmonary tuberculosis, on anti-tuberculosis therapy (att) for last 2 months who presented with fever, cough, breathlessness, anorexia, and weight loss. the case was found to be hiv reactive. his sputum sample showed candida albicans and pneumocystis jirovecii. fluconazole and cotrimoxazole + sulphamethoxazole were added. the index case did not respond to the treatment and his clinical condition started to deteriorate and he developed headache, vo ...201121460353
biochemical systems analysis of signaling pathways to understand fungal pathogenicity.over the past decade, researchers have recognized the need to study biological systems as integrated systems. while the reductionist approaches of the past century have made remarkable advances of our understanding of life, the next phase of understanding comes from systems-level investigations. additionally, biology has become a data-intensive field of research. the introduction of high throughput sequencing, microarrays, high throughput proteomics, metabolomics, and now lipidomics are producin ...201121468990
quantitation of cellular components in cryptococcus neoformans for system biology analysis.methods and procedures in molecular biology used to study fungal pathogenesis have significantly improved during the last decade. in this chapter, we provide step-by-step procedures for performing genetics and biochemical studies in the human pathogenic fungal microorganism cryptococcus neoformans (cn). these methods are employed for studying the pathobiology of cn and for experimental validation of theoretical models of fungal pathogenicity.201121468997
disseminated cryptococcosis in a non-hodgkin's lymphoma patient with late-onset neutropenia following rituximab-chop chemotherapy: a case report and literature review.rituximab-related late-onset neutropenia (r-lon) is an adverse event associated with rituximab. a 65-year-old woman presented with diffuse large b-cell lymphoma of the kidney without bone marrow involvement. she was treated with 4 cycles of chop chemotherapy consisting of doxorubicin, cyclophosphamide, vincristine, and prednisolone at 4-week intervals. rituximab was also administrated of the second, third, fourth chop cycles. she developed a high fever of 38°c, nausea, and severe neutropenia fol ...201121472389
disseminated histoplasma capsulatum and cryptococcus neoformans co-infection in patients with aids.histoplasmosis and cryptococcosis are the most prevalent systemic mycoses in hiv-infected patients. the authors report a 20-year-old brazilian hiv-positive woman with concomitant disseminated histoplasmosis and cryptococcosis. in addition, we review the reported cases described in the medical literature.201121472390
in vitro antifungal activities of amphotericin b in combination with acteoside, a phenylethanoid glycoside from colebrookea oppositifolia.the present study was undertaken to investigate the synergistic interaction between amphotericin b (amb) and acteoside, isolated from the aerial parts of colebrookea oppositifolia (lamiaceae). acteoside alone exhibited no intrinsic antifungal activity but it showed a potent synergism in combination with amb against selected pathogenic species, with fractional inhibitory concentration indices in the range of 0.0312 to 0.1562. the combination of 3.12 micrograms ml-1 and 12.5 micrograms ml-1 concen ...201121474610
the f-box protein fbp1 regulates sexual reproduction and virulence in cryptococcus neoformans.cryptococcus neoformans is the leading cause of fungal meningitis in immunocomprised populations. although extensive studies have been conducted on signal transduction pathways important for fungal sexual reproduction and virulence, how fungal virulence is regulated during infection is still not understood. in this study, we identified the f-box protein fbp1, which contains a putative f-box domain and 12 leucine-rich repeats (lrr). although fbp1 mutants showed normal growth and produced normal m ...201121478432
a novel specificity protein 1 (sp1)-like gene regulating protein kinase c-1 (pkc1)-dependent cell wall integrity and virulence factors in cryptococcus neoformans.eukaryotic cells utilize complex signaling systems to detect their environments, responding and adapting as new conditions arise during evolution. the basidiomycete fungus cryptococcus neoformans is a leading cause of aids-related death worldwide and utilizes the calcineurin and protein kinase c-1 (pkc1) signaling pathways for host adaptation and expression of virulence. in the present studies, a c-terminal zinc finger transcription factor, homologous both to the calcineurin-responsive zinc fing ...201121487010
the effect of the expression of virulence-associated dead-box rna helicase mrna on the imbalance of th1-th2 cytokines in the csf of patients with cryptococcus neoformans meningitis.virulence-associated dead-box rna helicase (vad1) is an important factor regulating the virulence of cryptococcus neoformans. we established a real-time quantitative polymerase chain reaction (pcr) assay to measure the expression of vad1 mrna in the cerebrospinal fluid (csf) of c. neoformans meningitis (cnm) patients, and we also detected the levels of ifn-γ, il-12 and il-10 proteins in these csf samples and controls. patients with head injuries were selected as controls. we found that the expre ...201121487762
cryptococcus peritonitis a rare manifestation in hiv positive host: a case report.cryptococcus neoformans is an encapsulated yeast found ubiquitously in the environment and causes serious infections in immunocompromised populations. disseminated disease is uncommon and very rarely manifests as peritonitis. we report a case of cryptococcal peritonitis in a hiv positive patient, who presented with distention of abdomen, vomiting, and dyspnoea, where the diagnosis was made on cytological smears of ascitic fluid. the importance of making a quick diagnosis utilizing cytological sm ...201121488179
regulation of copper homeostasis by cuf1 associates with its subcellular localization in the pathogenic yeast cryptococcus neoformans h99.here, we present further characterization of cryptococcal cuf1 in copper homeostasis. we demonstrated that cuf1 was involved both in copper acquisition and in copper detoxification in response to copper variation. this was verified by direct measurement of the quantity of intracellular copper with flame atomic absorption spectrometry (faas) and molecular evidence. in copper-limited growth, the mutant cuf1δ exhibited copper deficiency, growth defect on glycerol and sensitivity to hydrogen peroxid ...201121489137
synthesis and antifungal activity of functionalized 2,3-spirostane isomers.invasive fungal infections are a major complication for individuals with compromised immune systems. one of the most significant challenges in the treatment of invasive fungal infections is the increased resistance of many organisms to widely used antifungals, making the development of novel antifungal agents essential. many naturally occurring products have been found to be effective antimicrobial agents. in particular, saponins with spirostane glycosidic moieties-isolated from plant or marine ...201121489791
cryptococcal meningoencephalitis in a dog. 201121493445
larvicidal, antimicrobial and brine shrimp activities of extracts from cissampelos mucronata and tephrosia villosa from coast region, tanzania.abstract:201121513544
sulfonamides incorporating 1,3,5-triazine moieties selectively and potently inhibit carbonic anhydrase transmembrane isoforms ix, xii and xiv over cytosolic isoforms i and ii: solution and x-ray crystallographic studies.reaction of cyanuryl chloride with d,l-amino acids and amino alcohols afforded a new series of triazinyl-substituted benzenesulfonamides incorporating amino acyl/hydroxyalkyl-amino moieties. inhibition studies of physiologically relevant human carbonic anhydrase (ca, ec 4.2.1.1) isoforms, such as ca i, ii, ix, xii and xiv with these compounds are reported. they showed moderate-weak inhibition of the cytosolic, offtarget isozymes ca i and ii, but many of them were low nanomolar inhibitors of the ...201121515057
comparisons of clinical features and mortality of cryptococcal meningitis between patients with and without human immunodeficiency virus infection.background: cryptococcosis is a systemic infection caused by cryptococcus neoformans, and cryptococcal meningitis can occur in patients with late-stage human immunodeficiency virus (hiv) infection and other forms of immunosuppressive status. this study was designed to compare clinical features and laboratory findings of cryptococcal meningitis in hiv-positive and hiv-negative patients. methods: from january 1, 2000 to december 31, 2009, all patients aged more than 18 years hospitalized at nation ...201121524972
[mesenteric cryptococcal lymphadenitis: report of one case.]cryptococcosis is an invasive mycotic infection caused by cryptococcus neoformans, an encapsulated, yeast-like fungus. it is considered an opportunist infection, since it mainly affects immunocompromised subjects. however there are isolated reports of the infection in immunocompetent subjects. cryptococcal infection of intra-abdominal organs or tissues is extremely rare. we report a 21-year-old hiv positive male that, during the treatment of a meningeal cryptococcosis, presented a clinical pictu ...201121526303
small bowel perforation in a patient with aids. 201121530513
calcineurin controls drug tolerance, hyphal growth, and virulence in candida dubliniensis.candida dubliniensis is an emerging pathogenic yeast species closely related to candida albicans and frequently found colonizing or infecting the oral cavities of hiv/aids patients. drug resistance during c. dubliniensis infection is common and constitutes a significant therapeutic challenge. the calcineurin inhibitor fk506 exhibits synergistic fungicidal activity with azoles or echinocandins in the fungal pathogens c. albicans, cryptococcus neoformans, and aspergillus fumigatus. in this study, ...201121531874
hrk1 plays both hog1-dependent and -independent roles in controlling stress response and antifungal drug resistance in cryptococcus neoformans.the hog (high osmolarity glycerol response) pathway plays a central role in controlling stress response, ergosterol biosynthesis, virulence factor production, and differentiation of cryptococcus neoformans, which causes fatal fungal meningoencephalitis. recent transcriptome analysis of the hog pathway discovered a hog1-regulated gene (cnag_00130.2), encoding a putative protein kinase orthologous to rck1/2 in saccharomyces cerevisiae and srk1 in schizosaccharomyces pombe. its function is not know ...201121533251
antifungal susceptibilities of cryptococcus neoformans cerebrospinal fluid isolates from aids patients in kenya.poor susceptibility of cryptococcus neoformans to fluconazole (flc) is a matter of concern among clinicians in africa. the emergence of resistance to flc was recently reported in kenya, but it is not known whether it is widespread. thus, there is need for more antifungal drug susceptibility studies in kenya. the aim of this study was to measure the in vitro antifungal drug susceptibilities of incident c. neoformans isolates from acquired immunodeficiency syndrome patients in kenya. antifungal su ...201121535451
role for golgi reassembly and stacking protein (grasp) in polysaccharide secretion and fungal virulence.secretion of virulence factors is a critical mechanism for the establishment of cryptococcosis, a disease caused by the yeast pathogen cryptococcus neoformans. one key virulence strategy of c. neoformans is the release of glucuronoxylomannan (gxm), a capsule-associated immune-modulatory polysaccharide that reaches the extracellular space through secretory vesicles. golgi reassembly and stacking protein (grasp) is required for unconventional protein secretion mechanisms in different eukaryotic ce ...201121542865
improved identification of yeast species directly from positive blood culture media by combining sepsityper specimen processing and microflex analysis with the maldi biotyper system.current methods for identification of yeast from blood cultures may take several days after these microorganisms have been observed by gram-stain smears from positive blood cultures. we explored the use of a matrix-assisted laser desorption ionization (maldi) biotyper system in combination of sepsityper specimen processing and microflex analysis for improved detection and identification of yeast species directly from positive blood culture specimens demonstrating yeast-like organisms by gram-sta ...201121543564
cryptococcal-related exudative retinal detachment. 201121546919
root cultures of hypericum perforatum subsp. angustifolium elicited with chitosan and production of xanthone-rich extracts with antifungal activity.hypericum perforatum is a well-known medicinal plant which contains a wide variety of metabolites, including xanthones, which have a wide range of biological properties, including antifungal activity. in the present study, we evaluated the capability of roots regenerated from calli of h. perforatum subsp. angustifolium to produce xanthones. root biomass was positively correlated with the indole-3-butyric acid concentration, whereas a concentration of 1 mg l(-1) was the most suitable for the deve ...201121547455
efficient implementation of rna interference in the pathogenic yeast cryptococcus neoformans.an improved method has been developed for rna interference in cryptococcus neoformans, using opposing promoters to facilitate cloning and rna interference targeting ura5 to allow selection of cells in which silencing is most effective. these advances significantly reduce the variability of silencing and the effort required for interference plasmid construction.201121554906
cryptococcus neoformans mediator protein ssn8 negatively regulates diverse physiological processes and is required for virulence.cryptococcus neoformans is a ubiquitously distributed human pathogen. it is also a model system for studying fungal virulence, physiology and differentiation. light is known to inhibit sexual development via the evolutionarily conserved white collar proteins in c. neoformans. to dissect molecular mechanisms regulating this process, we have identified the ssn8 gene whose mutation suppresses the light-dependent cwc1 overexpression phenotype. characterization of sex-related phenotypes revealed that ...201121559476
genome-wide expression profiling of the response to short-term exposure to fluconazole in cryptococcus neoformans serotype a.abstract: background: fluconazole (flc), a triazole antifungal drug, is widely used for the maintenance therapy of cryptococcal meningoencephalitis, the most common opportunistic infection in aids patients. in this study, we examined changes in the gene expression profile of the c. neoformans reference strain h99 (serotype a) following flc treatment in order to investigate the adaptive cellular responses to drug stress. results: simultaneous analysis of over 6823 transcripts revealed that 476 ge ...201121569340
low diversity cryptococcus neoformans variety grubii multilocus sequence types from thailand are consistent with an ancestral african origin.the global burden of hiv-associated cryptococcal meningitis is estimated at nearly one million cases per year, causing up to a third of all aids-related deaths. molecular epidemiology constitutes the main methodology for understanding the factors underpinning the emergence of this understudied, yet increasingly important, group of pathogenic fungi. cryptococcus species are notable in the degree that virulence differs amongst lineages, and highly-virulent emerging lineages are changing patterns o ...201121573144
simultaneous central nervous system complications of c. neoformans infection.the most common neurological manifestation of cryptococcus neoformans infection is meningitis. other less common manifestations include parenchymal central nervous system (cns) granulomatous disease, hydrocephalus and stroke. c. neoformans is often suspected in immunodepressed patients, but it can be easily overlooked in otherwise healthy patients. this paper provides a detailed clinical description of a patient without immunosupression who developed multiple simultaneous neurological manifestat ...200921577360
new avenues for phage-display library to produce a cryptococcus-specific anti-idiotypic antibody of hm-1 killer toxin.existing antifungal drugs are notable for their inability to act rapidly, as well as their toxicity and limited spectrum. the identification of fungal-specific genes and virulence factors would provide targets for new and influential drugs. the display of repertories of antibody fragments on the surface of filamentous phage offers a new way to produce immunoreagents as defined specificities. here we report the selection of cryptococcus-specific targets by using phage-display panning from a cdna ...201121584874
structure-based design, synthesis and antifungal activity of new triazole derivatives.a series of new antifungal triazole derivatives with phenylacetamide side chain were rational designed and synthesized on the basis of the structural information of lanosterol 14α-demethylase (cyp51). in vitro antifungal activity assay indicated that several compounds showed higher activity than fluconazole. especially, compound 8h showed excellent inhibitory activity against candida albicans and cryptococcus neoformans (mic = 0.0156 μg/ml), suggesting that it is a promising lead for the develop ...201121585708
development of polymorphic microsatellite markers for cryptococcus neoformans.cryptococcus neoformans is a haploid basidiomycetous yeast that causes life-threatening infections in patients with and without impaired immune function. present typing systems for c. neoformans are limited by either poor standardization or high cost. we present eleven microsatellite loci that were developed from the published genomes of c. neoformans var. neoformans, and are applicable to the varieties and hybrids within c. neoformans.200821585994
evidence that the human pathogenic fungus cryptococcus neoformans var. grubii may have evolved in africa.most of the species of fungi that cause disease in mammals, including cryptococcus neoformans var. grubii (serotype a), are exogenous and non-contagious. cryptococcus neoformans var. grubii is associated worldwide with avian and arboreal habitats. this airborne, opportunistic pathogen is profoundly neurotropic and the leading cause of fungal meningitis. patients with hiv/aids have been ravaged by cryptococcosis - an estimated one million new cases occur each year, and mortality approaches 50%. u ...201121589919
[a case of secondary pulmonary cryptococcosis presenting with multiple cystic shadows].an 80-year-old woman with a history of rheumatoid arthritis and steroid diabetes had been given a diagnosis of multiple bilateral pulmonary cystic lesions 16 months previously, and these lesions were observed to gradually increase on follow-up. she presented with a fever of 38 degrees c, cough, and sputum for 2 weeks, and the pulmonary cystic lesions had enlarged, and therefore she was admitted. a chest x-ray film revealed multiple cystic lesions 4 cm in greatest dimension in both the left upper ...201121591463
treatment of rats with heat killed cells (hkc) of cryptococcus neoformans var. grubii induces cellular activation in spleen and lymphatic nodes.our previous studies showed that the subcutaneous pretreatment of rats with heat killed cells of cryptococcus neoformans (hkc) emulsified in complete freund adjuvant (cfa) promotes protection against an intraperitoneal challenge with viable c. neoformans. in this model, an appropriate activation of adherent peritoneal cells after antigenic treatment is very important for the control of the infection. here, we investigated the immune response developed in spleen and lymphatic nodes as a result of ...201121592577
rapid identification of cryptococcus neoformans var. grubii, c. neoformans var. neoformans, and c. gattii using rapid biochemical tests, differential media, and dna sequencing.rapid identification of cryptococcus neoformans var. grubii, cryptococcus neoformans var. neoformans, and cryptococcus gattii is imperative to facilitate prompt treatment of cryptococcosis and to understand the epidemiology of the disease. our purpose was to evaluate a test algorithm incorporating commercial rapid biochemical tests, differential media, and dna sequence analysis that will allow us to differentiate these taxa rapidly and accurately. we assessed 147 type, reference, and clinical is ...201121593254
a case of mania due to cryptococcal meningitis, successfully treated with adjunctive olanzapine, in a patient with acquired immunodeficiency syndrome.we report on the case of a patient with acquired immune deficiency syndrome- and cryptococcus neoformans meningitis-related mania in which olanzapine was successfully used adjunctively and transiently to antifungal therapy.201121601730
ccr4 promotes resolution of the er stress response during host temperature adaptation in cryptococcus neoformans.adaptation to host temperature is a prerequisite for any pathogen capable of causing deep infection in humans. our previous studies demonstrated that a cryptococcus neoformans ccr4δ mutant, lacking the major deadenylase involved in regulated mrna decay, was defective in host temperature adaptation and therefore, virulence. in this study, the ccr4δ mutant was found to exhibit characteristics of chronic upr engagement in both gene expression profile and phenotype. we demonstrate that host temperat ...201121602483
a critical role for fcgammariib in up-regulation of fas ligand induced by a microbial polysaccharide.the microbial capsular polysaccharide glucuronoxylomannan (gxm) from the opportunistic fungus cryptoccocus neoformans is able to alter the innate and adaptive immune response through multi-faceted mechanisms of immunosuppression. the ability of gxm to dampen the immune response involves the induction of t cell apoptosis, which is dependent on gxm-induced up-regulation of fas ligand (fasl) on antigen-presenting cells. in this study we elucidate the mechanism exploited by gxm to induce up-regulati ...201121605112
incubation of fungal cultures: how long is long enough?fungal cultures are traditionally incubated for 4 weeks or longer to maximise the recovery of slowly growing fungi. however, the data in support of this are scarce. the objectives of this study were to determine the optimum incubation time for specimens in which moulds or yeast are suspected and to review the literature. a total of 3036 fungal cultures of 2216 dermatological and 820 non-dermatological specimens were analysed. the day on which fungal growth was first noted, was recorded. eleven o ...201121605185
actin polymerization driven by wash causes v-atpase retrieval and vesicle neutralization before exocytosis.wasp and scar homologue (wash) is a recently identified and evolutionarily conserved regulator of actin polymerization. in this paper, we show that wash coats mature dictyostelium discoideum lysosomes and is essential for exocytosis of indigestible material. a related process, the expulsion of the lethal endosomal pathogen cryptococcus neoformans from mammalian macrophages, also uses wash-coated vesicles, and cells expressing dominant negative wash mutants inefficiently expel c. neoformans. d. d ...201121606208
a xylosylphosphotransferase of cryptococcus neoformans acts in protein o-glycan synthesis.cryptococcal meningoencephalitis is an aids-defining illness caused by the opportunistic pathogen cryptococcus neoformans. this organism possesses an elaborate polysaccharide capsule that is unique among pathogenic fungi and the glycobiology of c. neoformans has been a focus of research in the field. the capsule and other cellular glycans and glycoconjugates have been described, but the machinery responsible for their synthesis remains largely unexplored. we recently discovered xpt1p, an enzyme ...201121606487
cryptococcal endocarditis.fungal infections of the heart are increasingly described especially in immunocompromised patients. cardiac involvement can present with myocarditis, pericarditis or endocarditis. cryptococcal endocarditis is extremely rare, with only four reported cases in the literature. the prognosis, natural history and the optimal management for cryptococcal endocarditis are not well described because of paucity of cases. we report the case of a patient with prosthetic aortic valve endocarditis due to c. ne ...201121606721
characteristics and specificities of cryptococcus infections in french guiana, 1998-2008.cryptococcosis is a common opportunistic systemic mycosis caused by members of the encapsulated yeast genus cryptococcus. the aetiological agents of the disease are classified into two species, i.e., cryptococcus neoformans (serotypes a, d, and ad) affecting mainly immunocompromised patients and cryptococcus gattii (serotypes b and c) usually found in immunocompetent individuals. limited data exist on cryptococcus infections in french guiana, the department with the highest hiv incidence in the ...201121612563
case report-right iliac fossa mass in an hiv-positive woman. cryptococcal meningitis. 201021614883
antimicrobial activity of protease inhibitor from leaves of coccinia grandis (l.) voigt.antimicrobial activity of protease inhibitor isolated from coccinia grandis (l.) voigt. has been reported. a 14.3 kda protease inhibitor (pi) was isolated and purified to homogeneity by ammonium sulfate precipitation (20-85% saturation), sephadex g-75, deae sepharose column and trypsin-sepharose affinity chromatography from the leaves of c. grandis. the purity was checked by reverse phase high performance liquid chromatography. pi exhibited marked growth inhibitory effects on colon cell lines in ...201121615062
[laryngeal cryptococcosis: report of a case.] 201121616010
in vitro antifungal susceptibilities and molecular typing of sequentially isolated clinical cryptococcus neoformans strains from croatia.a collection of 48 clinical cryptococcus neoformans isolates from croatia were retrospectively investigated using in vitro antifungal susceptibility testing and molecular biological techniques to determine mating- and serotype by pcr as well as by amplified fragment length polymorphisms (aflp) genotyping. these isolates were obtained from fifteen patients, ten were hiv-negative (66.7%) and five were hiv-positive patients (33.3%). from five patients only one isolate was available, while from the ...201121617022
s100a10 downregulation inhibits the phagocytosis of cryptococcus neoformans by murine brain microvascular endothelial cells.cryptococcus neoformans invades the central nerve system through endocytosis by the vascular endothelia. s100a10 interacts with ca(2+) channel proteins in the vascular endothelia and regulates the filamentous actin network. we hypothesized that s100a10 was involved in the pathogenesis of cryptococcosis and sought to investigate here the effect on the phagocytosis and growth of c. neoformans of s100a10 downregulation by small interfering rna in murine brain microvascular endothelial cell (mbmecs) ...201121621598
detection and identification of probable endemic fungal pathogen, cryptococcus gattii, and worldwide pathogen, cryptococcus neoformans, by real-time pcr.a real-time pcr method for detection and identification of cryptococcus neoformans and cryptococcus gattii was developed and evaluated using dna from single-colony or koala nasal smears. two taqman minor groove binder probes that distinguished between these species were designed corresponding to the internal sequences of the cap59 gene for both species. the real-time pcr assay had 100% specificity, as assessed using 13 reference strains and 300 environmental strains. twelve smear samples from he ...201121623899
myasthenia gravis complicated with cryptococcal meningitis after thymectomy and long-term immunosuppressive therapy. 201121625779
genetic differentiation, recombination and clonal expansion in environmental populations of cryptococcus gattii in india.cryptococcus gattii is a ubiquitous eukaryotic pathogen capable of causing life-threatening infections in a wide variety of hosts, including both immunocompromised and immunocompetent humans. since infections by c. gattii are predominantly obtained from environmental exposures, understanding environmental populations of this pathogen is critical, especially in countries like india with a large population and with environmental conditions conducive for the growth of c. gattii. in this study, we a ...201121631689
gamma radiation interacts with melanin to alter its oxidation-reduction potential and results in electric current production.the presence of melanin pigments in organisms is implicated in radioprotection and in some cases, enhanced growth in the presence of high levels of ionizing radiation. an understanding of this phenomenon will be useful in the design of radioprotective materials. however, the protective mechanism of microbial melanin in ionizing radiation fields has not yet been elucidated. here we demonstrate through the electrochemical techniques of chronoamperometry, chronopotentiometry and cyclic voltammetry ...201121632287
phospholipids trigger cryptococcus neoformans capsular enlargement during interactions with amoebae and macrophages.a remarkable aspect of the interaction of cryptococcus neoformans with mammalian hosts is a consistent increase in capsule volume. given that many aspects of the interaction of c. neoformans with macrophages are also observed with amoebae, we hypothesized that the capsule enlargement phenomenon also had a protozoan parallel. incubation of c. neoformans with acanthamoeba castellanii resulted in c. neoformans capsular enlargement. the phenomenon required contact between fungal and protozoan cells ...201121637814
multiple roles of ypd1 phosphotransfer protein in viability, stress response, and virulence factor regulation in cryptococcus neoformans.ypd1 is a key phosphorelay protein that controls eukaryotic two-component systems, but its function is not known in cryptococcus neoformans. here, we report that ypd1 is required for viability of c. neoformans via the hog1 mapk pathway, but plays multiple cellular roles in both hog1-dependent and -independent manners.201121642509
[evaluation of the significance of molecular methods in the diagnosis of invasive fungal infections: comparison with conventional methods.]direct microscopy and culture methods are still valuable standard conventional methods for the diagnosis of infections caused by true or opportunistic fungal pathogens, especially in high risk patients. however, some of the problems concerning the application and interpretation of those methods, indicate a need for more rapid, practical and reliable tests with high sensitivity and specificity. this study was conducted to compare the results obtained by molecular methods with the results of conve ...201121644076
possible participation of the rho/rho-associated coiled-coil-forming kinase pathway in the cell death of cryptococcus neoformans caused by staphylococcus aureus adherence.we reported the apoptotic death of a fungus, cryptococcus (c.) neoformans, in response to adherence of the pathogenic bacterium staphylococcus (s.) aureus. in co-culture, cryptococcal actin was visibly aggregated. to investigate the mechanism of death, we considered the participation of small gtp-binding proteins belonging to the rho subfamily, which regulate the actin cytoskeleton. c. neoformans was cultured with s. aureus in the presence of n-(4-pyridyl)-4-(1-aminoethyl)cyclohexanecarboxamide ...201121645052
functional characterization of the ferroxidase, permease high-affinity iron transport complex from candida albicans.saccharomyces cerevisiae expresses two proteins that together support high-affinity fe-uptake. these are a multicopper oxidase, fet3p, with specificity towards fe(2+) and a ferric iron permease, ftr1p, which supports fe-accumulation. homologues of the genes encoding these two proteins are found in all fungal genomes including those for the pathogens, candida albicans and cryptococcus neoformans. at least one of these loci represents a virulence factor for each pathogen suggesting that this compl ...201121645130
regulatory circuitry governing fungal development, drug resistance, and disease.summary: pathogenic fungi have become a leading cause of human mortality due to the increasing frequency of fungal infections in immunocompromised populations and the limited armamentarium of clinically useful antifungal drugs. candida albicans, cryptococcus neoformans, and aspergillus fumigatus are the leading causes of opportunistic fungal infections. in these diverse pathogenic fungi, complex signal transduction cascades are critical for sensing environmental changes and mediating appropriate ...201121646428
cryptococcus neoformans requires a functional glycolytic pathway for disease but not persistence in the host.cryptococcus neoformans is an important fungal pathogen of immunocompromised individuals, with a close relative, cryptococcus gattii, emerging as a serious threat for the immunocompetent. during initial infection, c. neoformans colonizes the airspaces of the lungs, resulting in pneumonia, and subsequently migrates to the central nervous system (cns). we sought to understand fungal carbon utilization during colonization of these fundamentally different niches within the host, in particular the ro ...201121652778
rapid identification of cryptococcus neoformans and cryptococcus gattii by matrix-assisted laser desorption ionization-time of flight mass spectrometry.compared to dna sequence analysis, matrix-assisted laser desorption ionization-time of flight mass spectrometry (maldi-tof ms) correctly identified 100% of cryptococcus species, distinguishing the notable pathogens cryptococcus neoformans and c. gattii. identification was greatly enhanced by supplementing a commercial spectral library with additional entries to account for subspecies variability.201121653762
calcium signaling components in the human pathogen: cryptococcus neoformans.calcium signaling through calmodulin and the phosphatase calcineurin are required for key events of the biology of the human pathogen cryptococcus neoformans, including mating, morphogenesis, growth at 37°c and virulence. in a recent work we described the functional characterization of a new component of this calcium signaling network: the vacuolar calcium exchanger vcx1. this transporter is involved in calcium tolerance and virulence in c. neoformans. two other uncharacterized calcium transport ...201121655435
profiling a killer, the development of cryptococcus neoformans.the ability of fungi to transition between unicellular and multicellular growth has a profound impact on our health and the economy. many important fungal pathogens of humans, animals, and plants are dimorphic, and the ability to switch between morphological states has been associated with their virulence. cryptococcus neoformans is a human fungal pathogen that causes life-threatening meningoencephalitis in immunocompromised and, in some cases, immunocompetent hosts. cryptococcus neoformans grow ...201121658085
a survey of the in vitro antifungal activity of heather (erica sp.) organic honey.abstract monofloral heather (erica sp.) honey samples (n=89), harvested in portugal according to european organic beekeeping rules, were analyzed to test their antifungal effect against candida albicans, candida krusei, and cryptococcus neoformans. a synthetic honey solution was also tested to determine antifungal activity attributable to sugars. the specific growth rate (╬╝) values showed that growth of all the yeasts was reduced in the presence of honey. the honey concentration (% wt/vol) that ...201121663476
hiv-1 gp41 ectodomain enhances cryptococcus neoformans binding to human brain microvascular endothelial cells via gp41 core-induced membrane activities.cryptococcus neoformans causes life-threatening meningoencephalitis, particularly prevalent in aids patients. the interrelationship between c. neoformans and hiv-1 is intriguing, as both pathogens elicit severe neuropathological complications. we have previously demonstrated that the hiv-1 gp41 ectodomain fragments gp41-i33 (amino acids 579-611) and gp41-i90 (amino acids 550-639) can enhance c. neoformans binding to hbmecs (human brain microvascular endothelial cells). both peptides contain the ...201121668410
asymptomatic pulmonary cryptococcosis in a patient with crohn's disease on infliximab: case report. 201121674724
antimicrobial sesquiterpenoids from laurus nobilis l.activity-guided fractionations of leaf extracts from laurus nobilis l. led to the isolation of a known sesquiterpene lactone, deacetyl laurenobiolide (1). compound 1 showed antimicrobial activity against periopathic pathogens (actinomyces viscosus, porphyromonas gingivalis, prevotella intermedia and actinobacillus actinomycetemcomitans), opportunistic gram-positive bacteria (staphylococcus aureus and streptococcus pyogenes) and fungi (candida albicans, cryptococcus neoformans and aspergillus fum ...201121678158
posaconazole: a new antifungal weapon.the last twenty years, the incidence of invasive fungal infections (ifi) has risen dramatically due to the prolongation of survival of patients with multiple risk factors for fungal infections. amphotericin b was for more than 40 years the gold standard for almost all ifi, but toxicity and resistance, especially of new and emerging pathogens remained important issues. fluconazole and itraconazole have also the same disadvantage of resistance. voriconazole, a new triazole antifungal has offered a ...201121682687
unusual cause of cellulitis in a patient with hepatitis c and cirrhosis. 201121683822
role of phospholipases in fungal fitness, pathogenicity, and drug development - lessons from cryptococcus neoformans.many pathogenic microbes, including many fungi, produce phospholipases which facilitate survival of the pathogen in vivo, invasion and dissemination throughout the host, expression of virulence traits and evasion of host immune defense mechanisms. these phospholipases are either secreted or produced intracellularly and act by physically disrupting host membranes, and/or by affecting fungal cell signaling and production of immunomodulatory effectors. many of the secreted phospholipases acquire a ...201021687772
invasion of cryptococcus neoformans into human brain microvascular endothelial cells is mediated through the lipid rafts-endocytic pathway via the dual specificity tyrosine-phosphorylation-regulated kinase 3 (dyrk3).cryptococcus neoformans is a neurotropic fungal pathogen, which provokes the onset of devastating meningoencephalitis. we used human brain microvascular endothelial cells (hbmec) as the in vitro model to investigate how c. neoformans traverses across the blood-brain barrier. in this report, we present several lines of evidence indicating that c. neoformans invasion is mediated through the endocytic pathway via lipid rafts. human cd44 molecules from lipid rafts can directly interact with hyaluron ...201121693704
[Cryptococcal meningitis in children: description of 3 cases].Cryptococcal meningitis is much less common in children than adults. The purpose of this report is to describe 3 cases of cryptococcal meningitis observed in children admitted to the Neurology Department of the Fann University Hospital Center in Dakar, Senegal between July 2003 and November 2008. There were 2 girls whose ages were 8 and 15 years and one 9-year-old boy. All 3 patients presented acute or chronic meningoencephalitis. Diagnosis was based on direct microscopic examination of India in ...201121695878
monoclonal antibodies specific for immunorecessive epitopes of glucuronoxylomannan, the major capsular polysaccharide of cryptococcus neoformans, reduce serotype bias in an immunoassay for cryptococcal antigen.immunoassay for detection of glucuronoxylomannan (gxm), the major capsular polysaccharide of cryptococcus neoformans, is an important tool for diagnosis of cryptococcosis. however, immunoassays that are based solely or in part on detection with polyclonal antibodies may show serotype bias in detection of gxm, particularly limited sensitivity for serotype c. in this study, we describe detection of gxm in an antigen capture sandwich enzyme-linked immunosorbent assay (elisa) that used a cocktail of ...201121697342
Functional analysis of host factors that mediate the intracellular lifestyle of Cryptococcus neoformans.Cryptococcus neoformans (Cn), the major causative agent of human fungal meningoencephalitis, replicates within phagolysosomes of infected host cells. Despite more than a half-century of investigation into host-Cn interactions, host factors that mediate infection by this fungal pathogen remain obscure. Here, we describe the development of a system that employs Drosophila S2 cells and RNA interference (RNAi) to define and characterize Cn host factors. The system recapitulated salient aspects of fu ...201121698225
eosinophils contribute to il-4 production and shape the t-helper cytokine profile and inflammatory response in pulmonary cryptococcosis.susceptibility to infection with cryptococcus neoformans is tightly determined by production of il-4. in this study, we investigated the time course of il-4 production and its innate cellular source in mice infected intranasally with c. neoformans. we show that pulmonary il-4 production starts surprisingly late after 6 weeks of infection. interestingly, in the lungs of infected mice, pulmonary t helper (th) cells and eosinophils produce significant amounts of il-4. in eosinophil-deficient +ödblg ...201121699881
characterisation of clinical isolates of the cryptococcus neoformans-c. gattii species complex from the amazonas state in brazil.background: the differentiation and classification of pathogenic cryptococcus species provides useful data for epidemiological studies and for the clinical diagnosis and treatment of patients. objectives: the aim of this study was to characterise 40 clinical cryptococcus obtained from patients at the tropical medicine foundation of amazonas (fmtam) from 2006 to 2008. methods: it was used phenotypic (i.e., enzyme production and antifungal resistance) and molecular biological (ura5-rflp) experimen ...201121699993
cryptococcal meningitis in an hiv-negative patient with rheumatoid arthritis treated with rituximab. 201121700684
the effect of l-dopa on cryptococcus neoformans growth and gene expression.cryptococcus neoformans is unusual among melanotic fungi in that it requires an exogenous supply of precursor to synthesize melanin. c. neoformans melanizes during mammalian infection in a process that presumably uses host-supplied compounds such as catecholamines. l-3,4-dihydroxyphenylalanine (l-dopa) is a natural catecholamine that is frequently used to induce melanization in c. neoformans and l-dopa-melanized cryptococci manifest resistance to radiation, phagocytosis, detergents and heavy met ...201121705857
ptilomycalin a inhibits laccase and melanization in cryptococcus neoformans.the antifungal spirocyclic guanidine alkaloid, ptilomycalin a, from marine sponge monanchora arbuscula, inhibits melanogenesis of cryptococcus neoformans in vitro through inhibition of biosynthesis of laccase in the melanin biosynthetic pathway with an ic(50) of 7.3++m.201121715177
efficacy of intravenous amphotericin b-polybutylcyanoacrylate nanoparticles against cryptococcal meningitis in mice.amphotericin b deoxycholate (amb), a classic antifungal drug, remains the initial treatment of choice for deep fungal infections, but it is not appropriate for treatment of cryptococcal meningitis due to its inability to pass through the blood-brain barrier (bbb). we examined the efficacy of amphotericin b-polybutylcyanoacrylate nanoparticles (amb-pbca-nps) modified with polysorbate 80 that had a mean particle diameter less than 100 nanometers (69.0 -¦ 28.6 nm). amb-pbca-nps were detected in the ...201121720503
in vitro c3 deposition on cryptococcus capsule occurs via multiple complement activation pathways.complement can be activated via three pathways: classical, alternative, and lectin. cryptococcus gattii and cryptococcus neoformans are closely related fungal pathogens possessing a polysaccharide capsule composed mainly of glucuronoxylomannan (gxm), which serves as a site for complement activation and deposition of complement components. we determined c3 deposition on cryptococcus spp. by flow cytometry and confocal microscopy after incubation with serum from c57bl/6j mice as well as mice defic ...201121723612
calcineurin co-localizes with p-bodies and stress granules during thermal stress in cryptococcus neoformans.calcineurin is a calcium-calmodulin-activated serine-threonine specific phosphatase that operates during cellular responses to stress and plays a prominent role in transcriptional control whereas regulatory events beyond transcription are less well characterized. this study reveals a novel transcription-independent role of calcineurin during temperature-stress response in the human fungal pathogen cryptococcus neoformans. the diffusely cytoplasmic calcineurin catalytic subunit cna1 relocates to ...201121724937
identification of a zds-like gene zds3 as a new mediator of stress resistance, capsule formation and virulence of the human pathogenic yeast cryptococcus neoformans.the fungal zds proteins are regulators of the serine/threonine phosphatase 2a (pp2a) and the protein kinase a. here, we characterize a zds-like gene zds3 that plays a broad range of roles in the basidiomycetous pathogenic yeast cryptococcus neoformans. zds3 harbors the conserved activation domain zds_c of zds proteins. by gene disruption, zds3 is shown to play roles in capsule production, cell wall integrity, growth at a high temperature, resistance to h(2) o(2) stress, osmotic pressures and glu ...201121726407
meningitis caused by filobasidium uniguttulatum: case report and overview of the literature.cryptococcal meningitis is mainly caused by cryptococcus neoformans and cryptococcus gattii, but occasionally other cryptococcus species and phylogenetically related species are involved. herein, we present a case of cryptococcal meningitis from china, which was caused by an azole and flucytosine resistant filobasidium uniguttulatum. in addition, we present an overview of the literature of meningitis caused by cryptococcus species other than c. neoformans and c. gattii. eight cases were related ...201121729175
cryptococcus neoformans as a model for radioimmunotherapy of infections.there is an obvious and urgent need for novel approaches to treat infectious diseases. the use of monoclonal antibodies in therapy of infectious diseases is now experiencing renewed interest. during the last 5 years radioimmunotherapy (rit), a modality previously developed only for cancer treatment, has been successfully adapted for the treatment of experimental fungal, bacterial, and viral infections. as our model organism for studying the efficacy, mechanisms, potential toxicity, and radioresi ...201121747848
prognostic markers in aids-related cryptococcal meningitis.despite the advent and expanding access to antiretroviral therapy, hiv-associated cryptococcal meningitis (cm) remains a significant cause of mortality and morbidity amongst individuals with this infection in resource-limited settings.201121751623
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