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cryptococcus neoformans capsular enlargement and cellular gigantism during galleria mellonella infection.we have studied infection of cryptococcus neoformans in the non-vertebrate host galleria mellonella with particular interest in the morphological response of the yeast. inoculation of c. neoformans in caterpillars induced a capsule-independent increase in haemocyte density 2 h after infection. c. neoformans manifested a significant increase in capsule size after inoculation into the caterpillar. the magnitude of capsule increase depended on the temperature, being more pronounced at 37°c than at ...201121915338
Evaluation of the in vitro activity of amphotericin B by time-kill curve methodology against large and small capsulate C. neoformans isolates.We have evaluated and compared the activity of amphotericin B (AMB) by time-kill curve methodology against 20 clinical Cryptococcus neoformans isolates in which capsule induction in vitro was performed. Overall, large capsulated isolates were more resistant to killing by AMB over time when compared with those small capsulate ones.201121917396
iron influences the abundance of the iron regulatory protein cir1 in the fungal pathogen cryptococcus neoformans.the gata-type, zinc-finger protein cir1 regulates iron uptake, iron homeostasis and virulence factor expression in the fungal pathogen cryptococcus neoformans. the mechanisms by which cir1 senses iron availability, although as yet undefined, are important for understanding the proliferation of the fungus in mammalian hosts. we investigated the influence of iron availability on cir1 and found that the abundance of the protein decreases upon iron deprivation. this destabilization was influenced by ...201121963719
Multiple Disguises for the Same Party: The Concepts of Morphogenesis and Phenotypic Variations in Cryptococcus neoformans.Although morphological transitions (such as hyphae and pseudohyphae formation) are a common feature among fungi, the encapsulated pathogenic yeast Cryptococcus neoformans is found during infection as blastoconidia. However, this fungus exhibits striking variations in cellular structure and size, which have important consequences during infection. This review will summarize the main aspects related with phenotypic and morphological variations in C. neoformans, which can be divided in three classe ...201121922016
Fungal polysaccharides: biological activity beyond the usual structural properties.Studies on structure and function of polysaccharides in biological systems classically involve sequence and compositional analyses, anomeric configuration, type of glycosidic linkage, and presence of substituents. Recent studies, however, indicates that other structural parameters, so far little explored, can directly influence the biological activity of microbial polysaccharides. Among these parameters, we highlight the molecular dimensions of Cryptococcus neoformans polysaccharides, which appe ...201121886639
unravelling secretion in cryptococcus neoformans: more than one way to skin a cat.secretion pathways in fungi are essential for the maintenance of cell wall architecture and for the export of a number of virulence factors. in the fungal pathogen, cryptococcus neoformans, much evidence supports the existence of more than one route taken by secreted molecules to reach the cell periphery and extracellular space, and a significant degree of crosstalk between conventional and non-conventional secretion routes. the need for such complexity may be due to differences in the nature of ...201121898146
The casein kinase I protein Cck1 regulates multiple signaling pathways and is essential for cell integrity and fungal virulence in Cryptococcus neoformans.Casein kinases regulate a wide range of cellular functions in eukaryotes, including phosphorylation of proteins that are substrates for degradation via the ubiquitin-proteasome system (UPS). Our previous study demonstrated that Fbp1, a component of the SCF(FBP1) E3 ligase complex, was essential for Cryptococcus virulence. Because the Saccharomyces cerevisiae homolog of Fbp1, Grr1, requires casein kinase I (Yck1 and Yck2) to phosphorylate its substrates, we investigated the function of casein kin ...201121926330
The effects of gamma radiation, UV and visible light on ATP levels in yeast cells depend on cellular melanization.Previously we have shown that growth of melanized fungi is stimulated by low levels of gamma radiation. The goal of this study was to examine the effects of visible light, UV light, and gamma radiation on the energy level (ATP concentration) in melanized Cryptococcus neoformans cells. Melanized C. neoformans cells as well as non-melanized controls were subjected to visible, UV or gamma radiation, and ATP was quantified by measuring the amount of light emitted by the ATP-dependent reaction of luc ...201121944206
Antifungal activity and chemical composition of essential oils from Smyrnium olusatrum L. (Apiaceae) from Italy and Portugal.The essential oils and supercritical CO(2) extracts of wild Smyrnium olusatrum L. growing in Sardinia (Italy) and in Portugal were investigated. For the study, oils were isolated from total plant aerial part (umbels containing seeds). The content of ß-phellandrene (67.3% vs. 42.7%) and a-pinene (31.9% vs. 1.2%), respectively, the main components of Portuguese and Italian essential oils, declined during the maturation stage of the umbels. Contrarily, some other important components, particularly ...201121902563
pulmonary cryptococcosis.cryptococcosis is an invasive fungal infection (ifi), caused predominantly by cryptococcus neoformans or cryptococcus gattii, that affects both immunocompromised (ic) and non-ic patients. although the most serious disease manifestation is meningoencephalitis, cryptococcal pneumonia is underdiagnosed and may disseminate to the central nervous system (cns) and other sites depending upon host defenses and administration of appropriate antifungal therapy. the clinical presentation of pulmonary crypt ...201122167400
identification of novel mimicry epitopes for cardiac myosin heavy chain-α that induce autoimmune myocarditis in a/j mice.myocarditis is one cause of sudden cardiac death in young adolescents, and individuals affected with myocarditis can develop dilated cardiomyopathy, a frequent reason for heart transplantation. exposure to environmental microbes has been suspected in the initiation of heart autoimmunity, but the direct causal link is lacking. we report here identification of novel mimicry epitopes that bear sequences similar to those in cardiac myosin heavy chain (myhc)-α 334-352. these epitopes represent bacill ...201121939961
Ultrashort Peptide bioconjugates are exclusively antifungal agents and synergize with cyclodextrin and amphotericin B.Many natural broad-spectrum cationic antimicrobial peptides (AMPs) possess a general mode of action that is dependent on lipophilicity and charge. Modulating the lipophilicity of AMPs by the addition of a fatty acid has been an effective strategy to increase the lytic activity and can further broaden the spectrum of AMPs. However, lipophilic modifications that narrow the spectrum of activity and exclusively direct peptides to fungi are less common. Here, we show that short peptide sequences can ...201222006001
disease transmission from companion parrots to dogs and cats: what is the real risk?a number of common misconceptions exist regarding the degree of transmission from companion parrots to dogs and cats. concern regarding bacterial, viral, fungal, and parasitic transmission is generally unfounded, because disease transmission between companion parrots and dogs and cats is not well-documented. infections with mycobacterium spp, aspergillus spp, giardia spp, chlamydophila psittaci, salmonella spp, yersinia pseudotuberculosis, cryptococcus neoformans, histoplasma capsulatum, cryptos ...201122041215
TLR9-dependent activation of bone marrow-derived dendritic cells by URA5 DNA from Cryptococcus neoformans.Cryptococcus neoformans is an opportunistic fungal pathogen that causes meningoencephalitis in immunocompromised patients. Recently, we reported that TLR9 is involved in host defense against C. neoformans: specifically, it detects the pathogen's DNA. In the present study, we aimed to elucidate the mechanisms underlying TLR9-mediated activation of innate immune responses using the URA5 gene, which encodes a virulent component of this fungal pathogen. A PCR-amplified 345-bp URA5 gene fragment indu ...201122104112
Unique evolution of the UPR pathway with a novel bZIP transcription factor, Hxl1, for controlling pathogenicity of Cryptococcus neoformans.In eukaryotic cells, the unfolded protein response (UPR) pathway plays a crucial role in cellular homeostasis of the endoplasmic reticulum (ER) during exposure to diverse environmental conditions that cause ER stress. Here we report that the human fungal pathogen Cryptococcus neoformans has evolved a unique UPR pathway composed of an evolutionarily conserved Ire1 protein kinase and a novel bZIP transcription factor encoded by HXL1 (HAC1 and XBP1-Like gene 1). C. neoformans HXL1 encodes a protein ...201121852949
Generalized Cryptococcus albidus in an immunosuppressed patient with palmopustular psoriasis.Cryptococcal infection is relatively uncommon, except among immunocompromised individuals. The most common human pathogenic species is Cryptococcus neoformans. Virtually all organs can be affected, particularly the central nervous and pulmonary systems. The prototypical manifestations of cutaneous cryptococcal infection include generalized papules, periorificial acneiform pustules, and molluscumlike vesicles on the upper body. We describe an unusual case of Cryptococcus albidus infection present ...201122017065
[Pharmacokinetics of amphotericin B in the cerebrospinal fluid during continuous intrathecal administration for treatment of cryptococcal neoformans meningitis].To explore the pharmacokinetics of amphotericin B (AMB) in the cerebrospinal fluid (CSF) during continuous intrathecal administration of AMB for treatment of cryptococcal neoformans meningitis (CNM).201122126783
matrix-assisted laser desorption ionization-time of flight mass spectrometry identification of yeasts is contingent on robust reference spectra.matrix-assisted laser desorption ionization-time of flight mass spectrometry (maldi-tof ms) for yeast identification is limited by the requirement for protein extraction and for robust reference spectra across yeast species in databases. we evaluated its ability to identify a range of yeasts in comparison with phenotypic methods.201122022438
synthesis and antifungal activity of natural product-based 6-alkyl-2,3,4,5-tetrahydropyridines.seven 6-alkyl-2,3,4,5-tetrahydropyridines (5a-5g) that mimic the natural piperideines that were recently identified in fire ant venom have been synthesized. compounds 5c-5g with c-6 alkyl chain lengths from c14 to c18 showed varying degrees of antifungal activities, with 5e (6-hexadecyl-2,3,4,5-tetrahydropyridine) and 5f (6-heptadecyl-2,3,4,5-tetrahydropyridine) being the most active. compound 5e exhibited minimum fungicidal concentrations of 3.8, 15.0, 7.5, and 7.5 μg/ml against cryptococcus ne ...201121905650
invasive fungal infections in renal transplant recipients.invasive fungal infections are a significant and often lethal problem in transplant patients. infections caused by geographically limited endemic fungi are infrequent, and aspergillus species, mucorales species, candida species, and cryptococcus neoformans are the opportunistic fungi responsible for most such infections. the symptoms of systemic fungal infections are nonspecific, particularly in their early stages. the high rates of mortality and graft loss owing to fungal infections render earl ...201122142041
outcome of hiv-1-associated cryptococcal meningitis, denmark 1988?2008.abstract introduction: the risk of hiv-1-associated cryptococcus neoformans meningitis (cm) has decreased and the outcome has improved with the use of combination antiretroviral therapy (cart). outcome has not been reported in denmark in the cart era. methods: a review of all cases of hiv-1-associated cm treated at 2 hospitals in denmark was carried out. survival was compared by time-updated cox proportional hazards analysis. results: a total of 45 cases were evaluated. six individuals (13.3%) ...201122077922
Proteomic analysis of human umbilical vein endothelial cells incubated with Cryptococcus neoformans var. neoformans.Cryptococcus neoformans is a medically important fungus and can infect all the organs of the body. As vascular endothelial cell is an important target for C. neoformans to penetrate any organs, the differential protein expression of human umbilical vascular endothelial cell (HUVEC) after incubating with C. neoformans may be the key to penetration. The proteins of HUVECs incubated with C. neoformans and normal HUVECs were collected and purified. After two-dimensional electrophoresis, the differen ...201121910755
abc proteins in yeast and fungal pathogens.all fungal genomes harbour numerous abc (atp-binding cassette) proteins located in various cellular compartments such as the plasma membrane, vacuoles, peroxisomes and mitochondria. most of them have initially been discovered through their ability to confer resistance to a multitude of drugs, a phenomenon called pdr (pleiotropic drug resistance) or mdr (multidrug resistance). studying the mechanisms underlying pdr/mdr in yeast is of importance in two ways: first, abc proteins can confer drug res ...201121967054
catch me if you can: phagocytosis and killing avoidance by cryptococcus neoformans.after inhalation of infectious particles, cryptococcus neoformans resides in the alveolar spaces, where it can survive and replicate in the extracellular environment. this yeast has developed different mechanisms to avoid internalization by phagocytic cells, the main one being a polysaccharide capsule around the cell body, which inhibits the uptake of the yeast by macrophages. in addition, capsule-independent mechanisms have also been described, such as the production of antiphagocytic proteins. ...201122029633
epidemiology of bloodstream infections and predictive factors of mortality among hiv-infected adult patients in thailand in the era of highly active antiretroviral therapy.few studies have described the pattern of bloodstream infections (bsi) among hiv-infected patients in the highly active antiretroviral therapy (haart) era, particularly in resource-limited settings. a retrospective cohort study was conducted among 140 hiv-infected patients who had a positive blood culture from 2004-2008. of the 140 patients, 91 (65%) were male with a mean (sd) age of 38 (9.1) years and a median (iqr) cd4 cell count of 32 (9-112) cells/mm(3). community-acquired infection was ...201222274154
antibacterial effect and cytotoxicity of beta-1,3-1, 4-glucanase from endophytic bacillus subtilis swb8.we studied the antibiotic activity and selective cytotoxicity of beta-1,3-1,4-glucanase from endophytic bacillus subtilis swb8.201122260051
analysis of cell cycle and replication of mouse macrophages after in vivo and in vitro cryptococcus neoformans infection using laser scanning cytometry.we investigated the outcome of the interaction of cryptococcus neoformans (cn) with murine macrophages using laser scanning cytometry (lsc). previous results in our lab had shown that phagocytosis of cn promoted cell cycle progression. lsc allowed us to simultaneously measure the phagocytic index, macrophage dna content and 5-ethynyl-2' -deoxyuridine (edu) incorporation such that it was possible to study host cell division as a function of phagocytosis. lsc proved to be robust, reliable and high ...201222252872
antifungal activity of eugenol analogues. influence of different substituents and studies on mechanism of action.twenty one phenylpropanoids (including eugenol and safrole) and synthetic analogues, thirteen of them new compounds, were evaluated for antifungal properties, first with non-targeted assays against a panel of human opportunistic pathogenic fungi. some structure-activity relationships could be observed, mainly related to the influence of an allyl substituent at c-4, an oh group at c-1 and an och(3) at c-2 or the presence of one or two no(2) groups in different positions of the benzene ring. all a ...201222262200
capsules from pathogenic and non-pathogenic cryptococcus spp. manifest significant differences in structure and ability to protect against phagocytic cells.capsule production is common among bacterial species, but relatively rare in eukaryotic microorganisms. members of the fungal cryptococcus genus are known to produce capsules, which are major determinants of virulence in the highly pathogenic species cryptococcus neoformans and cryptococcus gattii. although the lack of virulence of many species of the cryptococcus genus can be explained solely by the lack of mammalian thermotolerance, it is uncertain whether the capsules from these organisms are ...201222253734
chronic suppurative cryptococcal extensor tenosynovitis in a patient with castleman's disease: a case report.cryptococcus neoformans is an ubiquitously occurring encapsulated fungus that is commonly found in the environment. it is also an opportunistic pathogen that has potential to cause systemic fungal infection, predominantly in the immunocompromised host with cell-mediated immunological defects. cryptococcal tenosynovitis is an extremely rare condition, with only a few cases previously documented in the literature. we report a case of chronic suppurative cryptococcal extensor tenosynovitis in a pat ...201123204976
mechanisms of uniparental mitochondrial dna inheritance in cryptococcus neoformans.in contrast to the nuclear genome, the mitochondrial genome does not follow mendelian laws of inheritance. the nuclear genome of meiotic progeny comes from the recombination of both parental genomes, whereas the meiotic progeny could inherit mitochondria from one, the other, or both parents. in fact, one fascinating phenomenon is that mitochondrial dna in the majority of eukaryotes is inherited from only one particular parent. typically, such unidirectional and uniparental inheritance of mitocho ...201122783110
the camp/protein kinase a pathway and virulence in cryptococcus neoformans.the basidiomycete fungus cryptococcus neoformans is an important pathogen of immunocompromised people. the ability of the fungus to sense its environment is critical for proliferation and the generation of infectious propagules, as well as for adaptation to the mammalian host during infection. the conserved camp/protein kinase a pathway makes an important contribution to sensing, as demonstrated by the phenotypes of mutants with pathway defects. these phenotypes include loss of the ability to ma ...201122783095
gene expression in fungi.this contribution is based on the four presentations made at the special interest group (sig) meeting titled gene expression in fungi held during imc9 in edinburgh. this overview is independent from other articles published or that will be published by each speaker. in the sig meeting, basic principles of in vivo animal models for virulence studies were discussed. infection associated genes of candida albicans and fungal adaptation to the host was summarized. azole susceptibility was evaluated a ...201122679585
species distribution and susceptibility profile of yeasts isolated from blood cultures: results of a multicenter active laboratory-based surveillance study in argentina.the mycology department of the instituto nacional de enfermedades infecciosas "dr. c. malbrán", conducted the second national multicenter survey on fungemia due to yeasts in argentina. the aim was to obtain updated data of the frequency of the causative species encountered and their in vitro susceptibility to seven antifungal agents. yeast species were identified by micromorphological and biochemical studies. antifungal susceptibility testing was performed by the reference microdilution method e ...201122430989
[neuromeningeal cryptococcosis in mali].cryptococcal meningitis is the most common fatal central nervous system infection in aids patients in sub-saharan africa. the purpose of this prospective study conducted from march 2003 to february 2004 in the internal medicine and infectious diseases departments of the point g university hospital center was to investigate the clinical, prognostic and epidemiological profile of cryptococcus neoformans infection in patients hospitalized for brain and meningeale infection (bmi). diagnosis of neuro ...201122393627
cryptococcus-related immune reconstitution inflammatory syndrome(iris): pathogenesis and its clinical implications.this review provides an overview of cryptococcus neoformans immunology and focuses on the pathogenesis of cryptococcus-related paradoxical immune reconstitution inflammatory syndrome (iris). cryptococcal iris has three phases: (1) before antiretroviral therapy (art), with a paucity of cerebrospinal fluid (csf) inflammation and defects in antigen clearance; (2) during initial art immune recovery, with pro-inflammatory signaling by antigen-presenting cells without an effector response; and (3) at ...201122389746
active pharmaceutical ingredient (api) from an estuarine fungus, microdochium nivale (fr.).various marine habitats sustain variety of bio-sources of ecological and biotech potentials. pharmaceutical potential compound cyclosporine a was reported from marine fungus microdochium nivale associated with porteresia coarctata, a marine salt marsh grass from mangrove environment distributed along the central west coast (cwc) of india. this study involves association of m. nivale with p. coarctata plant, fermentation conditions, purification of cyclosporine a, chemical characterization etc. i ...201122319884
isolated cryptococcal osteomyelitis in immunocompetent patient.cryptococcosis is a common opportunistic infection in aids patients. almost all cases present with meningitis with or without fungaemia. cryptococcal osteomyelitis occurs as part of a disseminated infection. isolated cryptococcal osteomyelitis is rare and more so in immunocompetent patients. a case of isolated osteomyelitis caused by cryptococcus neoformans in an immunocompetent patient is reported here. a female patient of 60 years old presented with pain and swelling of left clavicle. the hist ...201122315871
primay cutaneous cryptococcosis in an immunocompetent patient.the authors report a primary cutaneous cryptococcosis, caused by cryptococcus neoformans in immunocompetent patient, a farmer who developed extensive lesions at the site of an injury caused by one of the chickens on his right forearm, while he was cleaning out his barn. oral treatment with fluconazole was totally successful. a review of the literature showed the rarity of cutaneous cryptococcosis in immunocompetent patients and in contrast, that skin lesions frequently occur in immunocompromised ...201122281908
[agents by dimorphic fungi and cryptococcus neoformans infections]. 201122241269
a case of fluconazole, voriconazole-resistant cryptococcus neoformans isolated from and immunocompetent patient. 201122233828
antifungal activity of plumericin and isoplumericin.this study evaluated the in vitro antifungal activity of the chloroform extract of plumeria bicolor and its phytoconstituents plumericin and isoplumericin against candida species and cryptococcus neoformans by measuring the minimum inhibitory concentration (mic) and minimum fungicidal concentration (mfc). plumericin's consistently high activity against candida albicans, c. krusei, c. glabrata, c. tropicalis and cryptococcus neoformans was more potent than isoplumericin and the standard antifunga ...201122224260
antifungal effect of lavender honey against candida albicans , candida krusei and cryptococcus neoformans.monofloral lavender honey samples (n = 30), were analyzed to test antifungal effect against candida albicans, candida krusei, and cryptococcus neoformans. the specific growth rates (μ) showed that all the yeast growths were reduced in the presence of honey. the honey concentration (% w/v) that inhibited 10% of the yeasts growth (x min) ranged from 31.0% (c. albicans), 16.8% (c. krusei) and 23.0% (c. neoformans). a synthetic honey solution was also tested to determine antifungal activity attribut ...201123572800
bacterial and fungal meningitis and antimicrobial susceptibility pattern in tikur anbessa university hospital, addis ababa, ethiopia.meningitis is usually caused by viral, bacterial or fungal pathogens. bacterial meningitis is a medical emergency and if untreated has a high mortality rate. even among those who survive the infection, some may develop permanent neurological disorders.201123409400
[effect of 4b3 monoclonal antibody on the experimental cryptococcus neoformans infection].frequent relapses and high lethality of criptococcosis has encouraged the search for new therapeutic strategies.201123437519
[presumptive identification of cryptococcus gattii isolated from terminalia catappa in montería city, córdoba, colombia].the members of the cryptococcus neoformans species complex are responsible for cryptococcosis in animals and humans. human infection is thought to be acquired by inhalation of airborne propagules from an environmental source; therefore it is greatly important to study their habitat. objective: to determine the ecological relationship of cryptococcus gattii with terminalia catappa trees present in urban areas of montería city in colombia.201123437518
antimicrobial potential of selected brown seaweeds from vedalai coastal waters, gulf of mannar.to evaluate the antimicrobial activity of turbinaria conoides (t. conoides), padina gymnospora (p. gymnospora) and sargassum tenerrimum against human bacterial and fungal pathogens.201123569739
the antimicrobial activities of extract and compounds isolated from brillantaisia lamium.background:brillantaisia lamium is an erect branched herb, which grows to a height of 1.50 m in moist tropical areas, both in full sun and partial shade. in , the aerial part of this plant is used in the treatment of various microbial infections such as skin diseases and infections of urinary tract. the aim of this study was to evaluate the antimicrobial activities of ch(2)cl(2): meoh (1:1) extract, fractions and compounds from the aerial part of b. lamium.methods: the plant was dried and extrac ...201123365474
chronic meningitis: a diagnostic challenge highlighted in a case of cryptococcal meningoencephalitis in an apparently immunocompetent older woman.chronic meningitis can be difficult to diagnose. the authors report the case of an older caucasian lady, with no underlying immunocompromising factors, who presented with a 2 month history of confusion. due to the non-specific symptoms on presentation, a diagnosis was only obtained after a repeat ct scan of the brain, which showed hydrocephalus. subsequent cerebrospinal fluid analysis showed biochemical abnormalities and cryptococcus neoformans on staining.201122675017
in vitro antimicrobial activity of mangrove plant sonneratia alba.to investigate the antimicrobial property of mangrove plant sonneratia alba (s. alba).201223569943
seasonal prevalence of cryptococcus neoformans var. grubii and cryptococcus gattii inhabiting eucalyptus terreticornis and eucalyptus camaldulensis trees in jabalpur city of madhya pradesh, central india.this study presents a two-year retrospective analysis of the work done during 2003-2005 on the distribution population density and isolation frequency of cryptococcus neoformans var. grubii and cryptococcus gattii recovered from different parts of eucalyptus tree spp., at jabalpur madhya pradesh, central india. of the 1000 samples collected from bark, flowers, fruits, buds and leaves of eucalyptus trees e. terreticornis and e. camaldulensis, 32 (3.2%) were found to be positive for c.n var. grubi ...201223518169
in vitro antifungal activities of amphotericin b, 5-fluorocytosine, fluconazole and itraconazole against cryptococcus neoformans isolated from cerebrospinal fluid and blood from patients in serbia.recently, geographic variations in resistance to agents commonly used in the treatment of cryptococcosis have been reported. therefore, the antifungal susceptibilities of 31 clinical isolates of cryptococcus neoformans, collected in serbia during 10-year period, were investigated. strains were isolated from cerebrospinal fluid (n=28) and blood (n=3), from patients with aids (n=26), lymphoma (n=4) and kidney transplant recipient (n=1). the minimal inhibitory concentrations (mics) of amphotericin ...201223518082
epidemiology and molecular characterization of cryptococcus neoformans isolated from pigeon excreta in mazandaran province, northern iran.the aims of this study were to verify the presence of cryptococcus neoformans in pigeon excreta in mazandaran province, iran, to identify the varieties of the c. neoformans isolates using d1/d2 and igs sequencing, and determining the presence of the two mating types: α and a.201223518018
antifungal activity, sar and physicochemical correlation of some thiazole-1,3,5-triazine derivatives.present research communication was towards the investigation of antifungal minimum inhibitory concentration (mic) and minimum fingicidal concentration (mfc) activity of some substituted clubbed thiazole-1,3,5-triazines derivatives and effect of physicochemical properties on bioactivity.201223518015
biological activities of α-pinene and β-pinene enantiomers.the antimicrobial activities of the isomers and enantiomers of pinene were evaluated against bacterial and fungal cells. the agar diffusion test showed that only the positive enantiomers of the a- and β-isomers of pinene were active. the minimal inhibitory concentration (mic) and minimal microbicidal concentration (mmc) of these monoterpenes were also determined, confirming that the positive enantiomers exhibited microbicidal activity against all fungi and bacteria tested with mics ranging from ...201223442885
not all that shines is cancer: pulmonary cryptococcosis mimicking lymphoma in [(18)] f fluoro-2-deoxy-d-glucose positron emission tomography.we report of a case of pulmonary cryptococcosis mimicking lymphoma in a positron emission tomography (fdg-pet) scan. a 62-year old man with diffuse large b-cell lymphoma had complete resolution of abdominal and pulmonary lesions after three cycles of rituximab-based chemotherapy (r-chop). however, fdg-pet showed new pulmonary nodules, suggesting active lymphoma. chronic inflammatory granuloma was seen in the histopathological exam, with round-shaped structures compatible with fungus, later ident ...201223386093
two rare cases of central nervous system opportunistic mycoses.this article presents two cases of opportunistic mycoses (oms) of the central nervous system (cns) caused by cryptococcus neoformans and aspergillus nidulans, respectively. the patients were hospitalised in local hospitals between 2009 and 2011 because of unspecific symptoms (fever, headache, and/or weight lost). duration of symptoms varied from 4 days to over 2 weeks. the patients were treated with antibiotics and symptomatically. om was not suspected in any of them. the patients became critica ...201223334046
identification and functional demonstration of mirnas in the fungus cryptococcus neoformans.micrornas (mirnas), endogenous posttranscriptional repressors by base-pairing of their cognate mrnas in plants and animals, have mostly been thought lost in the kingdom of fungi. here, we report the identification of mirnas from the fungus cryptococcus neoformans. with bioinformatics and northern blotting approaches, we found that these mirnas and their hairpin precursors were present in this fungus. the size of mir1 and mir2 is 22 nt and 18 nt, respectively. the precursors are about ∼70 nt in l ...201223300755
approaching the functional annotation of fungal virulence factors using cross-species genetic interaction profiling.in many human fungal pathogens, genes required for disease remain largely unannotated, limiting the impact of virulence gene discovery efforts. we tested the utility of a cross-species genetic interaction profiling approach to obtain clues to the molecular function of unannotated pathogenicity factors in the human pathogen cryptococcus neoformans. this approach involves expression of c. neoformans genes of interest in each member of the saccharomyces cerevisiae gene deletion library, quantificat ...201223300468
[cryptococcus neoformans meningitis in children and adolescents infected with hiv].three cases of meningitis due to criptococcus in children infected with hiv are reported. all patients had severe immunodeficiency. the first case occurred before antiretroviral therapy. the second case had poor adherence to treatment. the third case is a teenager with prolonged fever, who did not have a clear source of transmission of hiv and was immunodeficient at the time of diagnosis. examination of cerebrospinal fluid with india ink dye was essential for making the diagnosis in all three ca ...201223282503
isolated skull cryptococcosis in an immunocompetent patient.a 62-year-old immunocompetent rural woman who represents an isolated cryptococcal skull infection without systematic involvement is described. diagnosis was based on positive india ink staining, positive histopathologic examination, and positive culture. species identification was performed by growth on sabouraud dextrose agar and chromagar medium and by sequencing of the intergenic and internal transcribed spacer regions of the rrna genes. this case describes a rare presentation of cryptococcus ...201223275242
structural and functional studies on a proline-rich peptide isolated from swine saliva endowed with antifungal activity towards cryptococcus neoformans.a proline-rich peptide of 2733da, isolated from pig parotid granule preparations was tested against different pathogenic fungi. it showed interesting antifungal activity towards a clinical isolate of cryptococcus neoformans, with an ec(50) of 2.2μm. neither cytotoxic nor haemolytic effects were observed towards mammalian cells. circular dichroism and infrared spectroscopic studies showed that the peptide adopted a combination of polyproline type-ii, β-turn and unordered conformations at physiolo ...201223274276
toxoplasma gondii: the effect of fluconazole combined with sulfadiazine and pyrimethamine against acute toxoplasmosis in murine model.toxoplasma gondii is an important opportunistic pathogen for immunocompromised patients and responsible for toxoplasmic encephalitis, which is often lethal. treatment for this infection is limited to a restricted therapeutic arsenal. in this work we tested the combination of fluconazole with the current treatment for acute toxoplasmosis on the murine model in vivo. different experimental groups were treated with combinations of sulfadiazine plus pyrimethamine with fluconazole and pyrimethamine w ...201223270807
cryptococcus neoformans growth and protection from innate immunity are dependent on expression of a virulence-associated dead-box protein, vad1.the fungus cryptococcus neoformans has emerged as a major cause of meningoencephalitis worldwide. host response to the fungus involves both innate and adaptive immunity, but fungal genes that modulate these processes are poorly understood. previous studies demonstrated attenuated virulence of a mutant of a virulence-associated dead-box protein (vad1) in mice, despite normal growth at host temperatures, suggesting modulation of the immune response. in the present study, the δvad1 mutant demonstra ...201223264050
induction of brain microvascular endothelial cell urokinase expression by cryptococcus neoformans facilitates blood-brain barrier invasion.the invasive ability of the blood-borne fungal pathogen cryptococcus neoformans can be enhanced through interactions with host plasma components, such as plasminogen. previously we showed by in vitro studies that plasminogen coats the surface of c. neoformans and is converted to the active serine protease, plasmin, by host plasminogen activators. viable, but not formaldehyde- or sodium azide-killed, cryptococcal strains undergo brain microvascular endothelial cell-dependent plasminogen-to-plasmi ...201223145170
allosteric regulation of lactobacillus plantarum xylulose 5-phosphate/fructose 6-phosphate phosphoketolase (xfp).xylulose 5-phosphate/fructose 6-phosphate phosphoketolase (xfp), which catalyzes the conversion of xylulose 5-phosphate (x5p) or fructose 6-phosphate (f6p) to acetyl phosphate, plays a key role in carbohydrate metabolism in a number of bacteria. recently, we demonstrated that the fungal cryptococcus neoformans xfp2 exhibits both substrate cooperativity for all substrates (x5p, f6p, and pi) and allosteric regulation in the forms of inhibition by phosphoenolpyruvate (pep), oxaloacetic acid (oaa), ...201525605308
molecular characterization of the early b cell response to pulmonary cryptococcus neoformans infection.the role of b cells in host defense against fungi has been difficult to establish. we quantified and determined the molecular derivation of b-1a, b-1b, and b-2 b cell populations in c57bl/6 mice after pulmonary infection with cryptococcus neoformans. total b-1 and b-2 cell numbers increased in lungs and peritoneal cavity as early as day 1 postinfection, but lacked signs of clonal expansion. labeled capsular (24067) and acapsular (cap67) c. neoformans strains were used to identify c. neoformans-b ...201223175699
purification, crystallization and preliminary x-ray analysis of adenylosuccinate synthetase from the fungal pathogen cryptococcus neoformans.with increasingly large immunocompromised populations around the world, opportunistic fungal pathogens such as cryptococcus neoformans are a growing cause of morbidity and mortality. to combat the paucity of antifungal compounds, new drug targets must be investigated. adenylosuccinate synthetase is a crucial enzyme in the atp de novo biosynthetic pathway, catalyzing the formation of adenylosuccinate from inosine monophosphate and aspartate. although the enzyme is ubiquitous and well characterize ...201323989157
bacterial etiologies of five core syndromes: laboratory-based syndromic surveillance conducted in guangxi, china.under the existing national surveillance system in china for selected infectious diseases, bacterial cultures are performed for only a small percentage of reported cases. we set up a laboratory-based syndromic surveillance system to elucidate bacterial etiologic spectrum and detect infection by rare etiologies (or serogroups) for five core syndromes in the given study area.201425360596
defects in phosphate acquisition and storage influence virulence of cryptococcus neoformans.nutrient acquisition and sensing are critical aspects of microbial pathogenesis. previous transcriptional profiling indicated that the fungal pathogen cryptococcus neoformans, which causes meningoencephalitis in immunocompromised individuals, encounters phosphate limitation during proliferation in phagocytic cells. we therefore tested the hypothesis that phosphate acquisition and polyphosphate metabolism are important for cryptococcal virulence. deletion of the high-affinity uptake system interf ...201424711572
factors required for activation of urease as a virulence determinant in cryptococcus neoformans.urease in cryptococcus neoformans plays an important role in fungal dissemination to the brain and causing meningoencephalitis. although urea is not required for synthesis of apourease encoded by ure1, the available nitrogen source affected the expression of ure1 as well as the level of the enzyme activity. activation of the apoenzyme requires three accessory proteins, ure4, ure6, and ure7, which are homologs of the bacterial urease accessory proteins ured, uref, and ureg, respectively. a yeast ...201323653445
experience with splenic abscess from southern india.splenic abscess is a rare entity with potentially life threatening complications. sparse recent published data are available documenting the aetiological profile and management of patients with splenic abscess from india.201627891372
a population-based acute meningitis and encephalitis syndromes surveillance in guangxi, china, may 2007-june 2012.acute meningitis and encephalitis (ame) are common diseases with the main pathogens being viruses and bacteria. as specific treatments are different, it is important to develop clinical prediction rules to distinguish aseptic from bacterial or fungal infection. in this study we evaluated the incidence rates, seasonal variety and the main etiologic agents of ame, and identified factors that could be used to predict the etiologic agents.201526633824
x-linked immunodeficient mice exhibit enhanced susceptibility to cryptococcus neoformans infection.abstract bruton's tyrosine kinase (btk) is a signaling molecule that plays important roles in b-1 b cell development and innate myeloid cell functions and has recently been identified as a target for therapy of b cell lymphomas. we examined the contribution of b-1 b cells to resistance to cryptococcus neoformans infection by utilizing x-linked immunodeficient (xid) mice (cba-cahn-xid), which possess a mutation in btk. xid mice had significantly higher brain fungal burdens than the controls 6 wee ...201323820392
the uve1 endonuclease is regulated by the white collar complex to protect cryptococcus neoformans from uv damage.the pathogenic fungus cryptococcus neoformans uses the bwc1-bwc2 photoreceptor complex to regulate mating in response to light, virulence and ultraviolet radiation tolerance. how the complex controls these functions is unclear. here, we identify and characterize a gene in cryptococcus, uve1, whose mutation leads to a uv hypersensitive phenotype. the homologous gene in fission yeast schizosaccharomyces pombe encodes an apurinic/apyrimidinic endonuclease acting in the uvde-dependent excision repai ...201324039606
structural determinants of oligomerization of δ(1)-pyrroline-5-carboxylate dehydrogenase: identification of a hexamerization hot spot.the aldehyde dehydrogenase (aldh) superfamily member δ(1)-pyrroline-5-carboxylate dehydrogenase (p5cdh) catalyzes the nad(+)-dependent oxidation of glutamate semialdehyde to glutamate, which is the final step of proline catabolism. defects in p5cdh activity lead to the metabolic disorder type ii hyperprolinemia, p5cdh is essential for virulence of the fungal pathogen cryptococcus neoformans, and bacterial p5cdhs have been targeted for vaccine development. although the enzyme oligomeric state is ...201323747974
concomitant cryptococcosis and burkholderia infection in an asymptomatic lung transplant patient with cystic fibrosis.concomitant pulmonary infections with cryptococcus neoformans and burkholderia cepacia in lung transplant recipients are very rare and create unique diagnostic and therapeutic dilemmas. herein, we present a double lung transplant patient with cystic fibrosis who was found to have coinfection with these two rare organisms, though he was completely asymptomatic.201025013584
pseudomonas aeruginosa inhibits the growth of scedosporium aurantiacum, an opportunistic fungal pathogen isolated from the lungs of cystic fibrosis patients.the filamentous fungus scedosporium aurantiacum and the bacterium pseudomonas aeruginosa are opportunistic pathogens isolated from lungs of the cystic fibrosis (cf) patients. p. aeruginosa has been known to suppress the growth of a number of cf related fungi such as aspergillus fumigatus, candida albicans, and cryptococcus neoformans. however, the interactions between p. aeruginosa and s. aurantiacum have not been investigated in depth. hence we assessed the effect of p. aeruginosa reference str ...201526379643
a multi-host approach for the systematic analysis of virulence factors in cryptococcus neoformans.a multi-host approach was followed to screen a library of 1201 signature-tagged deletion strains of cryptococcus neoformans mutants to identify previously unknown virulence factors. the primary screen was performed using a caenorhabditis elegans-c. neoformans infection assay. the hits among these strains were reconfirmed as less virulent than the wild type in the insect galleria mellonella-c. neoformans infection assay. after this 2-stage screen, and to prioritize hits, we performed serial evalu ...201425114160
radioimmunotherapy of cryptococcus neoformans spares bystander mammalian cells.previously, we showed that radioimmunotherapy (rit) for cryptococcal infections using radioactively labeled antibodies recognizing the cryptococcal capsule reduced fungal burden and prolonged survival of mice infected with cryptococcus neoformans. here, we investigate the effects of rit on bystander mammalian cells.201324020737
the role of amino acid permeases and tryptophan biosynthesis in cryptococcus neoformans survival.metabolic diversity is an important factor during microbial adaptation to different environments. among metabolic processes, amino acid biosynthesis has been demonstrated to be relevant for survival for many microbial pathogens, whereas the association between pathogenesis and amino acid uptake and recycling are less well-established. cryptococcus neoformans is an opportunistic fungal pathogen with many habitats. as a result, it faces frequent metabolic shifts and challenges during its life cycl ...201526162077
mitochondrial protein nfu1 influences homeostasis of essential metals in the human fungal pathogen cryptococcus neoformans.mitochondrial protein nfu1 plays an important role in the assembly of mitochondrial fe-s clusters and intracellular iron homeostasis in the model yeast saccharomyces cerevisiae. in this study, we identified the nfu1 ortholog in the human fungal pathogen cryptococcus neoformans. our data showed that c. neoformans nfu1 localized in the mitochondria and influenced homeostasis of essential metals such as iron, copper and manganese. marked growth defects were observed in the mutant lacking nfu1, whic ...201425606020
reactive oxygen species homeostasis and virulence of the fungal pathogen cryptococcus neoformans requires an intact proline catabolism pathway.degradation of the multifunctional amino acid proline is associated with mitochondrial oxidative respiration. the two-step oxidation of proline is catalyzed by proline oxidase and δ(1)-pyrroline-5-carboxylate (p5c) dehydrogenase, which produce p5c and glutamate, respectively. in animal and plant cells, impairment of p5c dehydrogenase activity results in p5c-proline cycling when exogenous proline is supplied via the actions of proline oxidase and p5c reductase (the enzyme that converts p5c to pro ...201323564202
cryptococcus neoformans activates rhogtpase proteins followed by protein kinase c, focal adhesion kinase, and ezrin to promote traversal across the blood-brain barrier.cryptococcus neoformans is an opportunistic fungal pathogen that causes meningoencephalitis. previous studies have demonstrated that cryptococcus binding and invasion of human brain microvascular endothelial cells (hbmec) is a prerequisite for transmigration across the blood-brain barrier. however, the molecular mechanism involved in the cryptococcal blood-brain barrier traversal is poorly understood. in this study we examined the signaling events in hbmec during interaction with c. neoformans. ...201222898813
novel cell-based in vitro screen to identify small-molecule inhibitors against intracellular replication of cryptococcus neoformans in macrophages.the fungal pathogen cryptococcus neoformans poses a major threat to immunocompromised patients and is a leading killer of human immunodeficiency virus (hiv)-infected patients worldwide. cryptococci are known to manipulate host macrophages and can either remain latent or proliferate intracellularly within the host phagocyte, a favourable niche that also renders them relatively insensitive to antifungal agents. here we report an attempt to address this limitation by using a fluorescence-based drug ...201627289450
persistence of nosocomial pathogens on various fabrics.fabrics can become contaminated with high numbers of microorganisms that may be pathogenic to patients in a hospital setting and can play an important role in the chain of infection. the aim of this study was to investigate the survival of several clinical bacterial and fungal isolates on several fabrics commonly used in hospitals.201225610201
cryptococcus neoformans promotes its transmigration into the central nervous system by inducing molecular and cellular changes in brain endothelial cells.cryptococcus spp. cause fungal meningitis, a life-threatening infection that occurs predominately in immunocompromised individuals. in order for cryptococcus neoformans to invade the central nervous system (cns), it must first penetrate the brain endothelium, also known as the blood-brain barrier (bbb). despite the importance of the interrelation between c. neoformans and the brain endothelium in establishing cns infection, very little is known about this microenvironment. here we sought to reso ...201323774597
aetiological agents of cerebrospinal meningitis: a retrospective study from a teaching hospital in ghana.meningitis is an important cause of morbidity and mortality in low-resource settings. in sub-saharan africa, the meningitis belt has been characterized by particularly high and seasonal incidences of bacterial meningitis extending throughout life. despite the progress being made in treating the condition, the mortality rates continue to be high, ranging between 2% and 30% globally. in ghana, the mortality rate of meningitis has been estimated to range from 36% to 50%. however little information ...201223035960
bacterial infections in lilongwe, malawi: aetiology and antibiotic resistance.life-threatening infections present major challenges for health systems in malawi and the developing world because routine microbiologic culture and sensitivity testing are not performed due to lack of capacity. use of empirical antimicrobial therapy without regular microbiologic surveillance is unable to provide adequate treatment in the face of emerging antimicrobial resistance. this study was conducted to determine antimicrobial susceptibility patterns in order to inform treatment choices and ...201222436174
a role for lhc1 in higher order structure and complement binding of the cryptococcus neoformans capsule.polysaccharide capsules are important virulence factors for many microbial pathogens including the opportunistic fungus cryptococcus neoformans. in the present study, we demonstrate an unusual role for a secreted lactonohydrolase of c. neoformans, lhc1 in capsular higher order structure. analysis of extracted capsular polysaccharide from wild-type and lhc1δ strains by dynamic and static light scattering suggested a role for the lhc1 locus in altering the capsular polysaccharide, both reducing di ...201424789368
through the wall: extracellular vesicles in gram-positive bacteria, mycobacteria and fungi.extracellular vesicles (evs) are produced by all domains of life. in gram-negative bacteria, evs are produced by the pinching off of the outer membrane; however, how evs escape the thick cell walls of gram-positive bacteria, mycobacteria and fungi is still unknown. nonetheless, evs have been described in a variety of cell-walled organisms, including staphylococcus aureus, mycobacterium tuberculosis and cryptococcus neoformans. these evs contain varied cargo, including nucleic acids, toxins, lipo ...201526324094
mechanisms by which interleukin-12 corrects defective nk cell anticryptococcal activity in hiv-infected patients.cryptococcus neoformans is a pathogenic yeast and a leading cause of life-threatening meningitis in aids patients. natural killer (nk) cells are important immune effector cells that directly recognize and kill c. neoformans via a perforin-dependent cytotoxic mechanism. we previously showed that nk cells from hiv-infected patients have aberrant anticryptococcal killing and that interleukin-12 (il-12) restores the activity at least partially through restoration of nkp30. however, the mechanisms ca ...201627555306
macrophage autophagy in immunity to cryptococcus neoformans and candida albicans.autophagy is used by eukaryotes in bulk cellular material recycling and in immunity to intracellular pathogens. we evaluated the role of macrophage autophagy in the response to cryptococcus neoformans and candida albicans, two important opportunistic fungal pathogens. the autophagosome marker lc3 (microtubule-associated protein 1 light chain 3 alpha) was present in most macrophage vacuoles containing c. albicans. in contrast, lc3 was found in only a few vacuoles containing c. neoformans previous ...201222710871
the role of dendritic cells in the innate recognition of pathogenic fungi (a. fumigatus, c. neoformans and c. albicans).dendritic cells (dcs) are the bridge between the innate and adaptive immune system. dcs are responsible for sensing and patrolling the environment, initiating a host response and instructing the proper adaptive immune response against pathogens. recent advances in medical treatments have led to increased use of immunosuppressive drugs, leading to the emergence of fungal species that cause life-threatening infections in humans. three of these opportunistic fungal pathogens: aspergillus fumigatus, ...201223076328
illuminating uveitis: metagenomic deep sequencing identifies common and rare pathogens.ocular infections remain a major cause of blindness and morbidity worldwide. while prognosis is dependent on the timing and accuracy of diagnosis, the etiology remains elusive in ~50 % of presumed infectious uveitis cases. the objective of this study is to determine if unbiased metagenomic deep sequencing (mds) can accurately detect pathogens in intraocular fluid samples of patients with uveitis.201627562436
reverse transcriptase and intron number evolution.introns are universal in eukaryotic genomes and play important roles in transcriptional regulation, mrna export to the cytoplasm, nonsense-mediated decay as both a regulatory and a splicing quality control mechanism, r-loop avoidance, alternative splicing, chromatin structure, and evolution by exon-shuffling.201427358863
new structural insights into golgi reassembly and stacking protein (grasp) in solution.among all proteins localized in the golgi apparatus, a two-pdz (psd95/dlga/zo-1) domain protein plays an important role in the assembly of the cisternae. this golgi reassembly and stacking protein (grasp) has puzzled researchers due to its large array of functions and relevance in golgi functionality. we report here a biochemical and biophysical study of the grasp55/65 homologue in cryptococcus neoformans (cngrasp). bioinformatic analysis, static fluorescence and circular dichroism spectroscopie ...201627436376
genomic insights into the atopic eczema-associated skin commensal yeast malassezia sympodialis.malassezia commensal yeasts are associated with a number of skin disorders, such as atopic eczema/dermatitis and dandruff, and they also can cause systemic infections. here we describe the 7.67-mbp genome of malassezia sympodialis, a species associated with atopic eczema, and contrast its genome repertoire with that of malassezia globosa, associated with dandruff, as well as those of other closely related fungi. ninety percent of the predicted m. sympodialis protein coding genes were experimenta ...201323341551
morphology and its underlying genetic regulation impact the interaction between cryptococcus neoformans and its hosts.cryptococcus neoformans is a fungus that causes the majority of fatal cryptococcal meningitis cases worldwide. this pathogen is capable of assuming different morphotypes: yeast, pseudohypha, and hypha. the yeast form is the most common cell type observed clinically. the hyphal and pseudohyphal forms are rarely observed in the clinical setting and are considered attenuated in virulence. however, as a ubiquitous environmental pathogen, cryptococcus interacts with various organisms, and it is known ...201525841056
fungal virulence in a lepidopteran model is an emergent property with deterministic features.abstract virulence has been proposed to be an emergent property, which by definition implies that it is not reducible to its components, but this application of a philosophical concept to the host-microbe interaction has not been experimentally tested. the goals of our study were to analyze the correlation of the phenotype with the ability to cause disease and to determine the dynamics of an experimental cryptococcal infection in galleria mellonella and acanthamoeba castellanii. by studying the ...201323631914
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