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classification of cryptococcus neoformans and yeast-like fungus isolates from pigeon droppings by colony phenotyping and its genotyping and their seasonal variations in korea.cryptococcus neoformans (c neoformans) is a frequent cause of invasive fungal disease in immunocompromised human hosts. ninety-eight samples of pigeon droppings were collected from the pigeon shelters in seoul, and cultured on birdseed agar (bsa) and sabouraud dextrose agar (sda). one hundred yeast-like colonies were selected and identified via phenotype characteristics, such as colony morphology and biochemical characteristics. this was then followed with genotyping via sequencing of the intern ...201222545529
function of cryptococcus neoformans kar7 (sec66) in karyogamy during unisexual and opposite-sex mating.the human basidiomycetous fungal pathogen cryptococcus neoformans serves as a model fungus to study sexual development and produces infectious propagules, basidiospores, via the sexual cycle. karyogamy is the process of nuclear fusion and an essential step to complete mating. therefore, regulation of nuclear fusion is central to understanding sexual development of c. neoformans. however, our knowledge of karyogamy genes was limited. in this study, using a blast search with the saccharomyces cere ...201222544906
titan cells confer protection from phagocytosis in cryptococcus neoformans infections.the human fungal pathogen cryptococcus neoformans produces an enlarged "titan" cell morphology when exposed to the host pulmonary environment. titan cells exhibit traits that promote survival in the host. previous studies showed that titan cells are not phagocytosed and that increased titan cell production in the lungs results in reduced phagocytosis of cryptococcal cells by host immune cells. here, the effect of titan cell production on host-pathogen interactions during early stages of pulmonar ...201222544904
kinetics of hiv-1 in cerebrospinal fluid and plasma in cryptococcal meningitis.in order to determine hiv-1 kinetics in cerebrospinal fluid (csf) and plasma in patients with cryptococcal meningitis (cm), we undertook a prospective collection of paired csf/plasma samples from antiretroviral therapy-free hiv-infected patients with cm. samples were obtained at baseline (s1) and at the second (s2) and third (s3) weeks of antifungal therapy. hiv-1 csf concentrations were significantly lower in both s2 and s3 with respect to s1. plasma concentrations remained stable. hiv-1 concen ...201224470944
cryptococcus neoformans/cryptococcus gattii species complex in southern italy: an overview on the environmental diffusion of serotypes, genotypes and mating-types.given the lack of comprehensive molecular epidemiology studies in reggio calabria and messina, italy, we decided to perform an extensive environmental sampling to describe the current molecular epidemiology of c. neoformans/c. gattii species complex in southern italy. in this study, we report the occurrence of serotypes, genotypes and mating-types of isolates of the c. neoformans/c. gattii species complex recovered from environmental sources. in addition, a number of environmental c. neoformans ...201222531979
capsule independent uptake of the fungal pathogen cryptococcus neoformans into brain microvascular endothelial cells.cryptococcosis is a life-threatening fungal disease with a high rate of mortality among hiv/aids patients across the world. the ability to penetrate the blood-brain barrier (bbb) is central to the pathogenesis of cryptococcosis, but the way in which this occurs remains unclear. here we use both mouse and human brain derived endothelial cells (bend3 and hcmec/d3) to accurately quantify fungal uptake and survival within brain endothelial cells. our data indicate that the adherence and internalisat ...201222530025
cerebral cryptococcomas in a cow.cerebral cryptococcomas are described in a 5-year-old mixed-breed cow without manifestations of systemic cryptococcosis. two cryptococcomas were observed grossly. microscopical examination revealed accumulations of yeast that were morphologically consistent with cryptococcus neoformans. immunohistochemistry characterized the organisms as c. neoformans var. grubii.201222520822
the antidepressant sertraline provides a promising therapeutic option for neurotropic cryptococcal infections.therapeutic treatment for systemic mycoses is severely hampered by the extremely limited number of antifungals. the difficulty of treatment of fungal infections in the central nervous system is further compounded by the poor central nervous system (cns) penetration of most antifungals due to the blood-brain barrier. only a few fungistatic azole drugs, such as fluconazole, show reasonable cns penetration. here we demonstrate that sertraline (zoloft), the most frequently prescribed antidepressant, ...201222508310
unraveling unique structure and biosynthesis pathway of n-linked glycans in human fungal pathogen cryptococcus neoformans by glycomics analysis.the encapsulated fungal pathogen cryptococcus neoformans causes cryptococcosis in immunocompromised individuals. although cell surface mannoproteins have been implicated in c. neoformans pathogenicity, the structure of n-linked glycans assembled on mannoproteins has not yet been elucidated. by analyzing oligosaccharide profiles combined with exoglycosidase treatment, we report here that c. neoformans has serotype-specific high mannose-type n-glycans with or without a β1,2-xylose residue, which i ...201222500028
[immune reconstitution inflammatory syndrome in cryptococcal meningitis: a rare phenomenon?].a 38-year old patient with previously untreated hiv infection presented with progressive cephalgia, photophobia, polydpsia and nausea/vomiting.201222495917
differences in nitrogen metabolism between cryptococcus neoformans and c. gattii, the two etiologic agents of cryptococcosis.two members of the cryptococcus neoformans-gattii species complex, the etiologic agents of cryptococcosis, can be differentiated by biological, biochemical, serological and molecular typing techniques. based on their differences in carbon and nitrogen utilization patterns, cost effective and very specific diagnostic tests using d-proline and canvanine-glycine-bromthymol blue (cgb) media have been formulated and are widely used for identification of the two species. however, these methods have ye ...201222479580
identification and molecular analysis of pathogenic yeasts in droppings of domestic pigeons in beijing, china.feral pigeons are known as reservoirs of pathogenic yeasts that cause opportunistic infections in human. in the outskirts of beijing, china, pigeons are more frequently raised at homes than are encountered in public areas. many studies have focused on the presence of pathogenic yeasts in the excreta (fresh or withered) of a variety kinds of birds, pigeon crop and cloacae. one hundred and forty-three samples of fresh droppings were collected from three suburban pigeon-raising homes in an area of ...201222476559
invasive fungal infection in chinese patients with systemic lupus erythematosus.invasive fungal infection (ifi) can be a lethal complication in systemic lupus erythematosus (sle). the aim of this study was to determine the characteristics of hospitalized sle patients with ifi, and identify the risk factors compared to sle with other major infections or those with active disease alone. data from 18 sle in-patients with ifi at shanghai renji hospital between january 2007 and january 2011 were collected by chart review. sle patients with either active mycobacterium tuberculosi ...201222476206
susceptibility to progressive cryptococcus neoformans pulmonary infection is regulated by loci on mouse chromosomes 1 and 9.genetic factors that regulate the pathogenesis of pneumonia caused by the fungus cryptococcus neoformans are poorly understood. through a phenotypic strain survey we observed that inbred c3h/hen mice develop a significantly greater lung fungal burden than mice of the resistant cba/j strain 4 weeks following intratracheal infection with c. neoformans atcc 24067. the aim of the present study was to characterize the inflammatory response of c3h/hen mice following c. neoformans pulmonary infection a ...201222988020
protective immunity against pulmonary cryptococcosis is associated with stat1-mediated classical macrophage activation.experimental pulmonary cryptococcus neoformans infection in balb/c mice is associated with polarized th2-type cytokine production, alternative macrophage activation, and severe bronchopneumonia. in contrast, pulmonary infection with a c. neoformans strain that secretes ifn-γ, h99γ, elicits th1-type cytokine production and classical macrophage activation. additionally, mice infected with h99γ resolve the acute infection and are subsequently protected against challenge with wild-type c. neoformans ...201222984078
a defect in iron uptake enhances the susceptibility of cryptococcus neoformans to azole antifungal drugs.the high-affinity reductive iron uptake system that includes a ferroxidase (cfo1) and an iron permease (cft1) is critical for the pathogenesis of cryptococcus neoformans. in addition, a mutant lacking cfo1 or cft1 not only has reduced iron uptake but also displays a markedly increased susceptibility to azole antifungal drugs. altered antifungal susceptibility of the mutants was of particular interest because the iron uptake system has been proposed as an alternative target for antifungal treatme ...201222975303
vaccine and immunotherapeutic approaches for the prevention of cryptococcosis: lessons learned from animal models.cryptococcus neoformans and c. gattii, the predominant etiological agents of cryptococcosis, can cause life-threatening infections of the central nervous system in immunocompromised and immunocompetent individuals. cryptococcal meningoencephalitis is the most common disseminated fungal infection in aids patients, and c. neoformans remains the third most common invasive fungal infection among organ transplant recipients. current anti-fungal drug therapies are oftentimes rendered ineffective due t ...201222973262
real-time in vivo imaging of fungal migration to the central nervous system.recent technical advances have afforded valuable new insights into the pathogenesis of fungal infections in the central nervous system (cns), which continue to cause devastating complications, particularly in immunocompromised individuals. to cause cns mycosis, organisms such as cryptococcus neoformans become blood borne and progress through a series of pathogenic checkpoints that culminate in fungal replication in the brain. critical steps include fungal arrest in the vasculature of the brain, ...201222966777
an antimicrobial evaluation of plants used for the treatment of respiratory infections in rural maputaland, kwazulu-natal, south africa.abundant availability of medicinal plants in the study area offers low cost health care, but scientific validation is needed in order to lend credibility to the traditional use against respiratory infections.201222960551
disseminated cryptococcosis in an immunocompetent patient: a case report.cryptococcus neoformans is ubiquitous encapsulated yeast found throughout the world. it predominantly causes significant infections in immunocompromised individuals, of which 80-90% occur in people with human immunodeficiency virus (hiv) infection. disseminated cryptococcal infection is uncommon and almost always occurs in hiv-infected patients. disseminated disease, especially noncutaneous cryptococcal abscess in immunocompetent hosts, is exceedingly rare. we report a case of disseminated crypt ...201222953139
cryptococcus neoformans-cryptococcus gattii species complex: an international study of wild-type susceptibility endpoint distributions and epidemiological cutoff values for fluconazole, itraconazole, posaconazole, and voriconazole.epidemiological cutoff values (ecvs) for the cryptococcus neoformans-cryptococcus gattii species complex versus fluconazole, itraconazole, posaconazole, and voriconazole are not available. we established ecvs for these species and agents based on wild-type (wt) mic distributions. a total of 2,985 to 5,733 clsi mics for c. neoformans (including isolates of molecular type vni [mics for 759 to 1,137 isolates] and vnii, vniii, and vniv [mics for 24 to 57 isolates]) and 705 to 975 mics for c. gattii ...201222948877
edta inhibits biofilm formation, extracellular vesicular secretion, and shedding of the capsular polysaccharide glucuronoxylomannan by cryptococcus neoformans.the fungal pathogen cryptococcus neoformans can grow as a biofilm on a range of synthetic and prosthetic materials. cryptococcal biofilm formation can complicate the placement of shunts used to relieve increased intracranial pressure in cryptococcal meningitis and can serve as a nidus for chronic infection. biofilms are generally advantageous to pathogens in vivo, as they can confer resistance to antimicrobial compounds, including fluconazole and voriconazole in the case of c. neoformans. edta c ...201222941091
effects of pimenta pseudocaryophyllus (gomes) l. r. landrum, on melanized and non-melanized cryptococcus neoformans.in the present study, the in vitro susceptibility and capsular width from both melanized and non-melanized cryptococcus neoformans cells in the presence of pimenta pseudocaryophyllus crude extract were determined. the results were compared with those obtained for voriconazole and amphotericin b. melanization was obtained in minimal medium broth with the addition of l-dopa, and the antifungal susceptibility tests were performed using the broth microdilution method. capsular width of 30 cells of e ...201222932958
central nervous system strongyloidiasis and cryptococcosis in an hiv-infected patient starting antiretroviral therapy.we report a case of strongyloides stercoralis hyperinfection syndrome with central nervous system involvement, in a patient with late human immunodeficiency virus (hiv) infection starting antiretroviral therapy, in whom strongyloides stercoralis larvae and cryptococcus neoformans were isolated antemortem from cerebrospinal fluid. our patient was not from an endemic region for the parasite, so strongyloidiasis was not originally suspected. for this reason, we conclude that strongyloides stercoral ...201222924046
[cryptococcal meningitis as initial presentation of systemic lupus erythematosus].infection is one of the most frequent etiology of morbidity and mortality in patients with systemic lupus erythematosus (sle). cryptococcal meningitis is a recognized complication of sle with high mortality rates in those treated with immunosuppressive agents. we describe a patient with cryptoccoccal meningitis and sle. this case suggests that intrinsic immunological abnormality related to sle predisposed to opportunistic infections.201222917073
transgene induced co-suppression during vegetative growth in cryptococcus neoformans.introduction of dna sequences into the genome often results in homology-dependent gene silencing in organisms as diverse as plants, fungi, flies, nematodes, and mammals. we previously showed in cryptococcus neoformans that a repeat transgene array can induce gene silencing at a high frequency during mating (∼50%), but at a much lower frequency during vegetative growth (∼0.2%). here we report a robust asexual co-suppression phenomenon triggered by the introduction of a cpa1::ade2 transgene. multi ...201222916030
[intraventricular cryptococcoma successfully treated with liposomal amphotericin b and voriconazole: a case report].cryptococcal infections of the central nervous system (cns) are infrequent in immunocompetent hosts and usually present as meningitis. however, fungal masses called cryptococcoma can sometimes be formed. we report a case in which intraventricular cryptococcoma in an immunocompetent patient was completely cured using liposomal amphotericin b (l-amb) and voriconazole (vrcz). a 56-year-old previously healthy man was admitted to our hospital with fever, headache and bilateral hand tremor lasting ove ...201222915699
influence of iron regulation on the metabolome of cryptococcus neoformans.iron is an essential nutrient for virtually all organisms and acts as a cofactor for many key enzymes of major metabolic pathways. furthermore, iron plays a critical role in pathogen-host interactions. in this study, we analyzed metabolomic changes associated with iron availability and the iron regulatory protein cir1 in a human fungal pathogen cryptococcus neoformans. our metabolite analysis revealed that cir1 influences the glycolytic pathway, ergosterol biosynthesis and inositol metabolism, w ...201222911836
main-chain imidazolium oligomer material as a selective biomimetic antimicrobial agent.human health has been challenged by multi-drug-resistant microorganisms for several decades. herein, we have developed a main-chain imidazolium oligomer (ibn-1) material to combat broad spectrum of pathogenic strains, including drug-resistant klebsiella pneumoniae, vancomycin-resistant enterococcus, methicillin-resistant staphylococcus aureus and fluconazole-resistant yeast cryptococcus neoformans, while displaying minimal hemolysis (hc(50)/mic values over 3000) and a very high therapeutic index ...201222902059
a defect in atp-citrate lyase links acetyl-coa production, virulence factor elaboration and virulence in cryptococcus neoformans.the interaction of cryptococcus neoformans with phagocytic cells of the innate immune system is a key step in disseminated disease leading to meningoencephalitis in immunocompromised individuals. transcriptional profiling of cryptococcal cells harvested from cell culture medium or from macrophages found differential expression of metabolic and other functions during fungal adaptation to the intracellular environment. we focused on the acl1 gene for atp-citrate lyase, which converts citrate to ac ...201223078142
mechanisms of infection by the human fungal pathogen cryptococcus neoformans.brain infection by the fungus cryptococcus neoformans results in inflammation of the meninges and brain parenchyma, a condition known as meningoencephalitis. one million people are estimated to suffer cryptococcal meningitis globally and >60% of these cases die within 3 months of diagnosis. humans are believed to contract infection by inhalation of spores or dried yeast cells, which subsequently colonize the lung tissue. in the lungs, cryptococci may be cleared by the lung phagocytes, stay laten ...201223075448
mechanisms of dendritic cell lysosomal killing of cryptococcus.cryptococcus neoformans is an opportunistic pulmonary fungal pathogen that disseminates to the cns causing fatal meningitis in immunocompromised patients. dendritic cells (dcs) phagocytose c. neoformans following inhalation. following uptake, cryptococci translocate to the dc lysosomal compartment and are killed by oxidative and non-oxidative mechanisms. dc lysosomal extracts kill cryptococci in vitro; however, the means of antifungal activity remain unknown. our studies determined non-oxidative ...201223074646
de novo gtp biosynthesis is critical for virulence of the fungal pathogen cryptococcus neoformans.we have investigated the potential of the gtp synthesis pathways as chemotherapeutic targets in the human pathogen cryptococcus neoformans, a common cause of fatal fungal meningoencephalitis. we find that de novo gtp biosynthesis, but not the alternate salvage pathway, is critical to cryptococcal dissemination and survival in vivo. loss of inosine monophosphate dehydrogenase (impdh) in the de novo pathway results in slow growth and virulence factor defects, while loss of the cognate phosphoribos ...201223071437
cryptococcosis.cryptococcosis is a systemic fungal infection, caused by encapsulated yeast of the genus cryptococcus, c neoformans and c gattii. these environmental microorganisms live in pigeon and other bird droppings, as well as in the fruit and bark of various trees. infection in humans and other animal species usually occurs by inhalation and less frequently through the skin and by ingestion of the fungus. most infections have a benign course and resolve spontaneously; however, the incidence of cryptococc ...201223068147
cryptococcus albidus infection in a california sea lion (zalophus californianus).sporadic cases of cryptococcosis have been reported in marine mammals, typically due to cryptococcus neoformans and, more recently, to cryptococcus gattii in cetaceans. cryptococcus albidus, a ubiquitous fungal species not typically considered to be pathogenic, was recovered from a juvenile california sea lion (zalophus californianus) rescued near san francisco bay, california. yeast morphologically consistent with a cryptococcus sp. was identified histologically in a lymph node and c. albidus w ...201223060504
prevalence of cryptococcosis among hiv-infected patients in yaounde, cameroon.cryptococcus neoformans is encapsulated yeast which causes life-threatening infections in up to 40% of aids patients in africa.201223056017
dna mutations mediate microevolution between host-adapted forms of the pathogenic fungus cryptococcus neoformans.the disease cryptococcosis, caused by the fungus cryptococcus neoformans, is acquired directly from environmental exposure rather than transmitted person-to-person. one explanation for the pathogenicity of this species is that interactions with environmental predators select for virulence. however, co-incubation of c. neoformans with amoeba can cause a "switch" from the normal yeast morphology to a pseudohyphal form, enabling fungi to survive exposure to amoeba, yet conversely reducing virulence ...201223055925
antifungal activity and composition of essential oils of conyza canadensis herbs and roots.essential oils from herbs and roots of conyza canadensis (horseweed), collected in hungary, were obtained by hydrodistillation. the chemical compositions of the oils were analysed by combination of gc and gc/ms. the major constituent of the oil obtained from the aerial parts of horseweed was limonene (78%), while the main component of root oil was 2z,8z-matricaria ester. the antimicrobial activities of the oils were tested on gram-positive (enterococcus faecalis, staphylococcus aureus, and strep ...201223049473
pleiotropic roles of the msi1-like protein msl1 in cryptococcus neoformans.msi1-like (msil) proteins contain wd40 motifs and have a pleiotropic cellular function as negative regulators of the ras/cyclic amp (camp) pathway and components of chromatin assembly factor 1 (caf-1), yet they have not been studied in fungal pathogens. here we identified and characterized an msil protein, msl1, in cryptococcus neoformans, which causes life-threatening meningoencephalitis in humans. notably, msl1 plays pleiotropic roles in c. neoformans in both camp-dependent and -independent ma ...201223042129
[invasive mycoses during hematopoietic stem cell transplantation].to define the frequency, etiology, and risk factors of invasive mycoses (im) in patients with allogeneic (allo) and autologous (auto) hematopoietic stem cell transplantation (hsct) and to evaluate the impact of im on overall survival (os).201223038972
antitumor, antibiotic and antileishmanial properties of the pyranonaphthoquinone psychorubrin from mitracarpus frigidus.the bioactivity guided fractionation of the dichloromethane extract of mitracarpus frigidus afforded the pyranonaphthoquinone psychorubrin. this compound, hitherto unknown in the genus mitracarpus, had its biological activity evaluated against one panel of bacteria and two fungi, three tumor cell lines (hl60, jurkat and mcf-7) and four leishmania species. its identity was confirmed unambiguously by (1)h, (13)c, (1)h-cosy, ir and uv-vis spectroscopy and mass spectrometry. psychorubrin displayed a ...201223037306
titan cell production enhances the virulence of cryptococcus neoformans.infection with cryptococcus neoformans begins when desiccated yeast cells or spores are inhaled and lodge in the alveoli of the lungs. a subset of cryptococcal cells in the lungs differentiate into enlarged cells, referred to as titan cells. titan cells can be as large as 50 to 100 μm in diameter and exhibit a number of features that may affect interactions with host immune defenses. to characterize the effect of titan cell formation on the host-pathogen interaction, we utilized a previously des ...201222890995
disseminated cryptococcal lymphadenitis with negative latex agglutination test.we reported an unusual case of disseminated cryptococcal lymphadenitis in an immunocompetent host who presented with fever and lymphadenopathy, which were the only two symptoms and signs. latex agglutination test of serum and cerebrospinal fluid (csf) were negative, while lymph node biopsy showed cryptococcus neoformans. a diagnosis of disseminated cryptococcal lymphadenitis was made. then the patient was treated with amphotericin b for 15 days as initial therapy and itraconazole for 6 months as ...201222882869
meningitis due to cryptococcus neoformans: treatment with posaconazole.central nervous system infections caused by cryptococcus neoformans remain to be opportunistic infections with high mortality in severely immunocompromised patients such as patients with aids. amphotericin b deoxycholate and fluconazole remain to be the drugs of choice; however, in consideration of the intolerance to amphotericin b deoxycholate and the possible resistance to fluconazole, it is necessary to evaluate other azoles, such as posaconazole, that have demonstrated lower adverse events. ...201222873639
terbinafine inhibits cryptococcus neoformans growth and modulates fungal morphology.cryptococcus neoformans is an encapsulated fungus that causes cryptococcosis. central nervous system infection is the most common clinical presentation followed by pulmonary, skin and eye manifestations. cryptococcosis is primarily treated with amphotericin b (amb), fluconazole (flc) and itraconazole (itc). in the present work, we evaluated the in vitro effect of terbinafine (trb), an antifungal not commonly used to treat cryptococcosis. we specifically examined the effects of trb, either alone ...201222850947
sarcoid-like reaction in cryptococcus neoformans infection.we report a patient with cryptococcus (c.) neoformans infection, who developed a case of sarcoid-like reaction (slr). there have been reports of slrs associated with malignancies. although differentiating sarcoidosis from slr is difficult, the patient was diagnosed as slr because propionibacterium acnes bacterial (pab) antibody staining of biopsy specimens was negative and the chest radiological findings improved after antifungal treatment. to our knowledge, this is the first report of slr occur ...201222847562
virulence factors identified by cryptococcus neoformans mutant screen differentially modulate lung immune responses and brain dissemination.deletions of cryptococcal pik1, rub1, and ena1 genes independently rendered defects in yeast survival in human csf and within macrophages. we evaluated virulence potential of these genes by comparing wild-type cryptococcus neoformans strain h99 with deletant and complement strains in a balb/c mouse model of pulmonary infection. survival of infected mice; pulmonary cryptococcal growth and pathology; immunological parameters; dissemination kinetics; and cns pathology were examined. deletion of eac ...201222846723
identification of fungal diseases at necropsy.the purpose of the death verification service is to elucidate the causes of deaths that occur without medical assistance and of ill-defined deaths. in recent decades, the epidemiological reality of fungal infections has changed due to the rise in opportunistic infections chiefly in immunocompromised patients. a study of fungal diseases in autopsies performed in the death verification service of the medicine school in são josé do rio preto between january 2000 and december 2009 was made. sixty-se ...201222840384
cryptococcal antigenemia in anti-retroviral naïve aids patients: prevalence and its association with cd4 cell count.cryptococcus neoformans is the most incriminated fungal pathogen causing meningitis in acquired immune deficiency syndrome (aids) patients, and is known to constitute a major cause of deaths in aids patients. this study aimed to determine the sero-prevalence and effect of cd4 count on seropositivity for cryptococcus neoformans antigen (crag) in antiretroviral- naïve (art-naïve) aids patients. this study included 150 (61 males and 89 females) art-naïve aids patients attending the human immunodefi ...201222837089
thirty year retrospective evaluation of pneumonia in a bottlenose dolphin tursiops truncatus population.pneumonia is one of the most common causes of morbidity in bottlenose dolphins tursiops truncatus. to better understand associations of pneumonia with demographics, microbiology, pathology, and histopathology, a retrospective study on 42 dolphins from the us navy marine mammal program dolphin population was conducted (1980 to 2010). a total of 21 (50%) of the dolphins evaluated had pneumonia confirmed by histopathology. bacterial and fungal pneumonia was present in 42.9 and 28.6% of cases (9 and ...201222832722
woodylides a-c, new cytotoxic linear polyketides from the south china sea sponge plakortis simplex.three new polyketides, woodylides a-c (1-3), were isolated from the ethanol extract of the south china sea sponge plakortis simplex. the structures were elucidated by spectroscopic data (ir, 1d and 2d nmr, and hresims). the absolute configurations at c-3 of 1 and 3 were determined by the modified mosher's method. antifungal, cytotoxic, and ptp1b inhibitory activities of these polyketides were evaluated. compounds 1 and 3 showed antifungal activity against fungi cryptococcus neoformans with ic₅₀ ...201222822354
screening for cryptococcal antigenemia in anti-retroviral naïve aids patients in benin city, nigeria.cryptococcus neoformans is the most incriminated fungal pathogen causing meningitis in acquired immune deficiency syndrome (aids) patients, and is known to constitute a major cause of deaths in aids patients. this study thus aimed to determine the baseline sero-prevalence of cryptococcus neoformans infection in anti-retroviral naïve (art-naïve) aids patients using the serum cryptococcal antigen (crag) detection method. baseline effect of variation in cd4 counts, as well as sex and age with sero- ...201222811773
rapid direct identification of cryptococcus neoformans from pigeon droppings by nested pcr using cnlac1 gene.isolation and identification of cryptococcus neoformans and pathogenic yeast-like fungi from pigeon droppings has been taken for a long time and requires various nutrients for its growth. in this study, we attempted to establish a rapid direct identification method of cr. neoformans from pigeon dropping samples by nested-pcr using internal transcribed spacer (its) cap64 and cnlac1 genes, polysaccharide capsule gene and laccase-associated gene to produce melanin pigment, respectively, which are c ...201222802194
gene conversion occurs within the mating-type locus of cryptococcus neoformans during sexual reproduction.meiotic recombination of sex chromosomes is thought to be repressed in organisms with heterogametic sex determination (e.g. mammalian x/y chromosomes), due to extensive divergence and chromosomal rearrangements between the two chromosomes. however, proper segregation of sex chromosomes during meiosis requires crossing-over occurring within the pseudoautosomal regions (par). recent studies reveal that recombination, in the form of gene conversion, is widely distributed within and may have played ...201222792079
a brain-vectored angiopep-2 based polymeric micelles for the treatment of intracranial fungal infection.one of the most common life-threatening infections in immunosuppressive patients, like aids patients, is cryptococcal meningitis or meningoencephalitis. current therapeutic options are mostly ineffective and mortality rates remain high. hydrophobic antifungal drug amphotericin b (amb), has become a golden standard in severe systemic fungal infection therapy. however, most amb commercial formulations, including deoxycholate amb and lipid formulations of amb, show poor penetration into the cns and ...201222789719
[pattern recognition and host defense response to cryptococcus neoformans].cryptococcus neoformans is an opportunistic fungal pathogen that causes fatal meningoencephalitis in immunocompromised hosts such as patients with aids and hematological malignancy. host defense to c. neoformans infection is mediated by th1-type cellular immunity, which is triggered by host cell recognition of the pathogen-associated molecular patterns via the pattern recognition receptors. recently, our study revealed that tlr9-dependent sensing of cryptococcal dna was a pivotal step in initiat ...201223257725
[a case of pulmonary cryptococcus neoformans infection]. 201223257048
the crz1/sp1 transcription factor of cryptococcus neoformans is activated by calcineurin and regulates cell wall integrity.cryptococcus neoformans survives host temperature and regulates cell wall integrity via a calcium-dependent phosphatase, calcineurin. however, downstream effectors of c. neoformans calcineurin are largely unknown. in s. cerevisiae and other fungal species, a calcineurin-dependent transcription factor crz1, translocates to nuclei upon activation and triggers expression of target genes. we now show that the c. neoformans crz1 ortholog (crz1/sp1), previously identified as a protein kinase c target ...201223251520
a mistaken diagnosis of molluscum contagiosum in a hiv-positive patient in rural south africa.a 25-year-old gentleman presented with multiple small ulcerations and papules covering a large portion of his face and neck, associated with general malaise. he was hiv seropositive with a total cd4 count of 78 cells/µl. a diagnosis of molluscum contagiosum was made and the patient discharged. he re-presented 3 weeks later with a 2-day history of progressively worsening headache associated with photophobia and diarrhoea. the generalised skin eruption had worsened, now involving his torso and upp ...201223242094
a human fungal pathogen cryptococcus neoformans expresses three distinct iron permease homologs.iron plays a key role in host-pathogen interactions. microbial pathogens require iron for survival and virulence, whereas mammalian hosts sequester and withhold iron as a means of nutritional immunity. we previously identified two paralogous genes, cft1 and cft2, which encode homologs of a fungal iron permease, cft1 and cft2, respectively, in the human fungal pathogen cryptococcus neoformans. cft1 was shown to play a role in the high-affinity reductive iron uptake system, and was required for tr ...201223221526
depletion of neutrophils in a protective model of pulmonary cryptococcosis results in increased il-17a production by γδ t cells.protective responses in mice immunized with an interferon-gamma producing strain of cryptococcus neoformans, h99γ, are associated with il-17a production by neutrophils. neutrophil depletion in h99γ-immunized mice did not affect pulmonary fungal burden, indicating that neutrophils are not required for clearance. however, we observed an increase in il-17a in the lungs of neutrophil-depleted h99γ infected mice, which corresponded to an increase in il-17a+ γδ+ t cells. moreover, we observed increase ...201223216912
central nervous system cryptococcosis among a cohort of hiv infected patients from a university hospital of north india.cryptococcus neoformans is a ubiquitous encapsulated yeast that causes significant infections which range from asymptomatic pulmonary colonization to the life threatening meningoencephalitis, especially in immunocompromised individuals. cryptococcal meningitis is one of the aids-defining illnesses. recent data have indicated that, the incidence of the cryptococcal infection is high in developing countries like india. we conducted this study to find out the incidence of cryptococcosis in this are ...201223205353
clinical utility of the cryptococcal antigen lateral flow assay in a diagnostic mycology laboratory.cryptococcus neoformans causes life-threatening meningitis. a recently introduced lateral flow immunoassay (lfa) to detect cryptococcal antigen (crag) is reportedly more rapid and convenient than standard latex agglutination (la), but has not yet been evaluated in a diagnostic laboratory setting.201223166705
detection of invasive fungal pathogens by real-time pcr and high-resolution melting analysis.causative agents most frequently encountered in systemic infections are bacteria, although fungi that cause invasive infections have also emerged, mostly in immune-compromised patients. the early detection and adequate treatment of bloodstream infections are critical for successful treatment. the aim of this study was to develop a rapid and efficient method for the detection and differentiation of the most common fungal pathogens.201223160681
antimicrobial activities of endophytic fungi isolated from ophiopogon japonicus (liliaceae).drug resistance in bacteria has become a global concern and the search for new antibacterial agents is urgent and ongoing. endophytes provide an abundant reservoir of bioactive metabolites for medicinal exploitation, and an increasing number of novel compounds are being isolated from endophytic fungi. ophiopogon japonicus, containing compounds with antibacterial activity, is a traditional chinese medicinal plant used for eliminating phlegm, relieving coughs, latent heat in the lungs, and allevia ...201223190550
aimless mutants of cryptococcus neoformans: failure to disseminate.the pathogenic fungus cryptococcus neoformans exhibits a striking propensity to cause central nervous system (cns) disease in people with hiv/aids. given that cryptococcal infections are generally initiated by pulmonary colonization, dissemination requires that the fungus withstand phagocytic killing, cross the alveolar-capillary interface in the lung, survive in the circulatory system and breach the blood-brain barrier. we know little about the molecular mechanisms underlying dissemination, but ...201223189087
cryptococcus neoformans-derived microvesicles enhance the pathogenesis of fungal brain infection.cryptococcal meningoencephalitis is the most common fungal disease in the central nervous system. the mechanisms by which cryptococcus neoformans invades the brain are largely unknown. in this study, we found that c. neoformans-derived microvesicles (cnmvs) can enhance the traversal of the blood-brain barrier (bbb) by c. neoformans invitro. the immunofluorescence imaging demonstrates that cnmvs can fuse with human brain microvascular endothelial cells (hbmecs), the constituents of the bbb. this ...201223144903
[dermatomycoses due to pets and farm animals : neglected infections?].dermatomycoses due to contact with pets and livestock frequently affect children and young adults. zoophilic dermatophytes are the main important causative agents. it has long been known that the often high inflammatory dermatophytoses of the skin and the scalp are caused mostly by microsporum canis. due to an absence of an obligation for reporting fungal infections of the skin to the public health office in germany, an unnoticed but significant change in responsible pathogens has occurred. toda ...201223114507
lymphocyte transformation assay for c neoformans antigen is not reliable for detecting cellular impairment in patients with neurocryptococcosis.cryptococcus neoformans causes meningitis and disseminated infection in healthy individuals, but more commonly in hosts with defective immune responses. cell-mediated immunity is an important component of the immune response to a great variety of infections, including yeast infections. we aimed to evaluate a specific lymphocyte transformation assay to cryptococcus neoformans in order to identify immunodeficiency associated to neurocryptococcosis (ncc) as primary cause of the mycosis.201223110700
immune modulation mediated by cryptococcal laccase promotes pulmonary growth and brain dissemination of virulent cryptococcus neoformans in mice.c. neoformans is a leading cause of fatal mycosis linked to cns dissemination. laccase, encoded by the lac1 gene, is an important virulence factor implicated in brain dissemination yet little is known about the mechanism(s) accounting for this observation. here, we investigated whether the presence or absence of laccase altered the local immune response in the lungs by comparing infections with the highly virulent strain, h99 (which expresses laccase) and mutant strain of h99 deficient in laccas ...201223110112
disseminated cryptococcosis in an hiv-positive boy.cryptococcosis is rare among children, only occurring in about 1% of children with hiv. we report the case of a 12-year-old boy with disseminated cryptococcosis. he had a history of recurrent pneumonia. he then developed meningeal symptoms and was found to have disseminated cryptococcus neoformans by cerebrospinal fluid and bone marrow aspirate culture. he was treated with amphotericin b for 2 weeks (1 mg/kg/day), and then with fluconazole orally for 8 weeks (12 mg/kg/day). he also received a ne ...201223104630
a three-step culture system to increase the xanthone production and antifungal activity of hypericum perforatum subsp. angustifolium in vitro roots.hypericum perforatum is a well-known medicinal plant. among all secondary metabolites produced by this species, xanthones are very interesting for their antifungal activity. in the present study, with the aim to improve xanthone production and antifungal activity of h. perforatum subsp. angustifolium (sin. fröhlich) borkh in vitro roots, a new methodology consisting of a three-step culture system, has been developed. regenerated roots of h. perforatum were cultured in a three-step culture system ...201222677450
cryptococcus neoformans carried by odontomachus bauri ants.cryptococcus neoformans is the most common causative agent of cryptococcosis worldwide. although this fungus has been isolated from a variety of organic substrates, several studies suggest that hollow trees constitute an important natural niche for c. neoformans. a previously surveyed hollow of a living pink shower tree (cassia grandis) positive for c. neoformans in the city of rio de janeiro, brazil, was chosen for further investigation. odontomachus bauri ants (trap-jaw ants) found inside the ...201222666855
maldi-tof ms enables the rapid identification of the major molecular types within the cryptococcus neoformans/c. gattii species complex.the cryptococcus neoformans/c. gattii species complex comprises two sibling species that are divided into eight major molecular types, c. neoformans vni to vniv and c. gattii vgi to vgiv. these genotypes differ in host range, epidemiology, virulence, antifungal susceptibility and geographic distribution. the currently used phenotypic and molecular identification methods for the species/molecular types are time consuming and expensive. as matrix-assisted laser desorption ionization-time-of-flight ...201222666368
cryptococccal meningoencephalitis after h1n1 influenza.cryptococcus neoformans is associated with a spectrum of diseases including meningoencephalitis, pneumonia and soft tissue infections. incidence is higher in immunocompromised hosts like hiv-infected individuals and solid organ transplant recipients. the influenza virus is known to cause immunologic defects. additionally, the 2009-pandemic h1n1 virus is associated with increased incidence of acute respiratory distress syndrome (ards) requiring treatment with systemic steroids. the authors presen ...201222665712
significance of antibody detection in the diagnosis of cryptococcal meningitis.cryptococcus neoformans is the causative agent of cryptococcosis, a chronic and life-threatening infection common in aids patients. sonicated proteins of cryptococci were reported to contain antigenic properties. in the present study antigens are prepared from cryptococcal culture filtrate and by sonication. secretory antigens are prepared by precipitation of culture filtrate using saturated ammonium sulfate followed by dialysis. prepared antigens are tested for the presence of antibodies in the ...201222471604
characterization of an nmr homolog that modulates gata factor-mediated nitrogen metabolite repression in cryptococcus neoformans.nitrogen source utilization plays a critical role in fungal development, secondary metabolite production and pathogenesis. in both the ascomycota and basidiomycota, gata transcription factors globally activate the expression of catabolic enzyme-encoding genes required to degrade complex nitrogenous compounds. however, in the presence of preferred nitrogen sources such as ammonium, gata factor activity is inhibited in some species through interaction with co-repressor nmr proteins. this regulator ...201222470421
analysis of cryptococcus neoformans sexual development reveals rewiring of the pheromone-response network by a change in transcription factor identity.the fundamental mechanisms that control eukaryotic development include extensive regulation at the level of transcription. gene regulatory networks, composed of transcription factors, their binding sites in dna, and their target genes, are responsible for executing transcriptional programs. while divergence of these control networks drives species-specific gene expression that contributes to biological diversity, little is known about the mechanisms by which these networks evolve. to investigate ...201222466042
prostaglandin e2 suppresses antifungal immunity by inhibiting interferon regulatory factor 4 function and interleukin-17 expression in t cells.t helper 17 (th17) cells play an important role in mucosal host defense through production of the signature cytokines il-17 and il-22. prostaglandin e2 (pge2) has been shown to enhance il-17 production by mature th17 cells. however, when present during th17 cell differentiation, we found that pge2 inhibited the transcription factor irf4 and suppressed production of il-17 but not il-22. we show that irf4 was required for il-17 expression but inhibited il-22 expression, highlighting the potential ...201222464170
the chitin connection.chitin, a polymer of n-acetylglucosamine, is an essential component of the fungal cell wall. chitosan, a deacetylated form of chitin, is also important in maintaining cell wall integrity and is essential for cryptococcus neoformans virulence. in their article, gilbert et al. [n. m. gilbert, l. g. baker, c. a. specht, and j. k. lodge, mbio 3(1):e00007-12, 2012] demonstrate that the enzyme responsible for chitosan synthesis, chitin deacetylase (cda), is differentially attached to the cell membrane ...201222448043
extensive genetic diversity within the dutch clinical cryptococcus neoformans population.a set of 300 dutch cryptococcus neoformans isolates, obtained from 237 patients during 1977 to 2007, was investigated by determining the mating type, serotype, and aflp and microsatellite genotype and susceptibility to seven antifungal compounds. almost half of the studied cases were from hiv-infected patients, followed by a patient group of individuals with other underlying diseases and immunocompetent individuals. the majority of the isolates were mating type α and serotype a, followed by αd i ...201222442325
cryptococcal osteomyelitis of the scapula and rib in an immunocompetent patient.cryptococcal osteomyelitis is extremely rare and almost always occurs in immunocompromised patients. we describe a case of osteomyelitis due to cryptococcus neoformans involving both scapula and rib in an immunocompetent and previously healthy patient. the patient received treatment with amphotericin b deoxycholate and flucytosine for 4 weeks, followed by oral fluconazole 400 mg per day for 8 weeks and 200 mg per day for 9 months. the 12-month course of antifungal therapy resulted in complete cl ...201222435878
resistance of asian cryptococcus neoformans serotype a is confined to few microsatellite genotypes.cryptococcus neoformans is a pathogenic yeast that causes cryptococcosis, a life threatening disease. the prevalence of cryptococcosis in asia has been rising after the onset of the aids epidemic and estimates indicate more than 120 cases per 1,000 hiv-infected individuals per year. almost all cryptococcal disease cases in both immunocompromised and immunocompetent patients in asia are caused by c. neoformans var. grubii. epidemiological studies on c. neoformans in pan-asia have not been reporte ...201222427900
difference in cryptococcus neoformans cellular and capsule size in sequential pulmonary and meningeal infection: a postmortem study.cryptococcus neoformans is an encapsulated yeast that primarily causes a life-threatening meningoencephalitis in immunosuppressed individuals especially those with hiv/aids. its main virulence factor is its polysaccharide capsule which interferes with complement-mediated phagocytosis. c. neoformans infections ensue following inhalation of small desiccated less encapsulated propagules leading to pulmonary pneumonia or colonization of the host's respiratory tract. numerous murine experimental stud ...201222424901
early induction of ccl7 downstream of tlr9 signaling promotes the development of robust immunity to cryptococcal infection.we investigated mechanisms by which tlr9 signaling promoted the development of the protective response to cryptococcus neoformans in mice with cryptococcal pneumonia. the afferent (week 1) and efferent (week 3) phase immune parameters were analyzed in the infected wild-type (tlr9(+/+)) and tlr-deficient (tlr9(-/-)) mice. tlr9 deletion diminished 1) accumulation and activation of cd11b(+) dendritic cells (dcs), 2) the induction of ifn-γ and ccr2 chemokines ccl7, ccl12, but not ccl2, at week 1, an ...201222422883
adjunctive interferon-γ immunotherapy for the treatment of hiv-associated cryptococcal meningitis: a randomized controlled trial.interferon-gamma (ifnγ) is of key importance in the immune response to cryptococcus neoformans. mortality related to cryptococcal meningitis remains high, and novel treatment strategies are needed. we performed a randomized controlled trial to determine whether addition of ifnγ to standard therapy increased the rate of clearance of cryptococcal infection in hiv-associated cryptococcal meningitis.201222421244
hyaluronic acid receptor cd44 deficiency is associated with decreased cryptococcus neoformans brain infection.cryptococcus neoformans is a pathogenic yeast that can invade the brain and cause meningoencephalitis. our previous in vitro studies suggested that the interaction between c. neoformans hyaluronic acid and human brain endothelial cd44 could be the initial step of brain invasion. in this report, we used a cd44 knock-out (ko or cd44(-/-)) mouse model to explore the importance of cd44 in c. neoformans brain invasion. our results showed that c. neoformans-infected cd44 ko mice survived longer than t ...201222418440
antifungal peptides at membrane interaction.many drugs are available for the treatment of systemic or superficial mycoses, but only a limited number of them are effective antifungal drugs, devoid of toxic and undesirable side effects. furthermore, resistance development and fungistatic rather than fungicidal activities represent limitations of current antifungal therapy. therefore an urgent need for a new generation of antifungal agents remains. we recently synthesised a set of linear and cyclic peptides characterized by sequences typical ...201222417640
characterization of the chromosome 4 genes that affect fluconazole-induced disomy formation in cryptococcus neoformans.heteroresistance in cryptococcus neoformans is an intrinsic adaptive resistance to azoles and the heteroresistant phenotype is associated with disomic chromosomes. two chromosome 1 (chr1) genes, erg11, the fluconazole target, and afr1, a drug transporter, were reported as major factors in the emergence of chr1 disomy. in the present study, we show chr4 to be the second most frequently formed disomy at high concentrations of fluconazole (flc) and characterize the importance of resident genes cont ...201222412978
isolated biliary cryptococcosis manifesting as obstructive jaundice in an immunocompetent adult.cryptococcosis is a symptomatic fungal infection caused by cryptococcus, which frequently occurs in patients who are immunologically compromised or chronically ill. localized involvement of the hepatobiliary system in an immunocompetent adult is extremely rare. we report a unique case of isolated biliary cryptococcosis manifesting as obstructive jaundice and mimicking hilar cholangiocarcinoma in an immunocompetent woman. by integrating surgical and antifungal drug therapy, the disease was effect ...201222408568
fungal-induced cell cycle impairment, chromosome instability and apoptosis via differential activation of nf-κb.microbial pathogens have developed efficient strategies to compromise host immune responses. cryptococcus neoformans is a facultative intracellular pathogen, recognised as the most common cause of systemic fungal infections leading to severe meningoencephalitis, mainly in immunocompromised patients. this yeast is characterized by a polysaccharide capsule, which inhibits its phagocytosis. whereas phagocytosis escape and macrophage intracellular survival have been intensively studied, extracellula ...201222396644
research trends on pathogenic cryptococcus species in the last 20 years: a global analysis with focus on brazil.recent data demonstrates that cryptococcosis caused by cryptococcus neoformans or cryptococcus gattii kills approximately 600,000 people per year in the world. in brazil, cryptococcosis has recently been identified as the most fatal mycosis in aids patients. in this study, we aimed to map research into c. neoformans and c. gattii in the world, with a focus on the brazilian contribution to this area.201222393887
cryptococcus neoformans-cryptococcus gattii species complex: an international study of wild-type susceptibility endpoint distributions and epidemiological cutoff values for amphotericin b and flucytosine.clinical breakpoints (cbps) are not available for the cryptococcus neoformans-cryptococcus gattii species complex. mic distributions were constructed for the wild type (wt) to establish epidemiologic cutoff values (ecvs) for c. neoformans and c. gattii versus amphotericin b and flucytosine. a total of 3,590 amphotericin b and 3,045 flucytosine clsi mics for c. neoformans (including 1,002 vni isolates and 8 to 39 vnii, vniii, and vniv isolates) and 985 and 853 mics for c. gattii, respectively (in ...201222391546
genetic diversity and genomic plasticity of cryptococcus neoformans ad hybrid strains.natural hybridization between two strains, varieties, or species is a common phenomenon in both plants and animals. although hybridization may skew established gene pools, it generates population diversity efficiently and sometimes results in the emergence of newly adapted genotypes. cryptococcus neoformans, which causes the most frequent opportunistic fungal infection in immunocompromised hosts, has three serotypes: a, d, and ad. serotype-specific multilocus sequence typing and serotype-specifi ...201222384385
population genetic analyses reveal the african origin and strain variation of cryptococcus neoformans var. grubii. 201222383873
[fungal infection induced by cryptococcus neoformans aerosol inhalation in immunosuppressed balb/c mice].to explore the feasibility of inducing fungal infection by cryptococcus neoformans aerosol inhalation in immunosuppressed balb/c mice.201222381750
a murine model of cryptococcus gattii meningoencephalitis.meningoencephalitis caused by cryptococcus gattii is associated with significant morbidity and the need for aggressive therapy, and often necessitates neurosurgical intervention. we adapted a previously described murine model of cryptococcal meningoencephalitis due to cryptococcus neoformans to that caused by c. gattii.201222378683
a unique chromosomal rearrangement in the cryptococcus neoformans var. grubii type strain enhances key phenotypes associated with virulence.the accumulation of genomic structural variation between closely related populations over time can lead to reproductive isolation and speciation. the fungal pathogen cryptococcus is thought to have recently diversified, forming a species complex containing members with distinct morphologies, distributions, and pathologies of infection. we have investigated structural changes in genomic architecture such as inversions and translocations that distinguish the most pathogenic variety, cryptococcus n ...201222375073
transplacental transmission of cryptococcus neoformans to an hiv-exposed premature neonate.cryptococcosis during pregnancy is well documented, but transmission of infection to the fetus is rare. we describe a premature neonate born to a mother with congenitally acquired human immunodeficiency virus (hiv) and active cryptococcosis. histological examination of the placenta revealed cryptococcus neoformans within the maternal intervillous space with focal invasion into the chorionic villi. a positive serum cryptococcal antigen (1:2) was detected on days 1 and 5 of life. the neonate had n ...201222370896
experimental methodologies and evaluations of computer-aided drug design methodologies applied to a series of 2-aminothiophene derivatives with antifungal activities.fifty 2-[(arylidene)amino]-4,5-cycloalkyl[b]thiophene-3-carbonitrile derivatives were screened for their in vitro antifungal activities against candida krusei and cryptococcus neoformans. based on experimentally determined minimum inhibitory concentration (mic) values, we conducted computer-aided drug design studies [molecular modelling, chemometric tools (cpca, pca, pls) and qsar-3d] that enable the prediction of three-dimensional structural characteristics that influence the antifungal activit ...201222367025
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