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nonlytic exocytosis of cryptococcus neoformans from macrophages occurs in vivo and is influenced by phagosomal ph.abstract a unique aspect of the interaction of the fungus cryptococcus neoformans with macrophages is the phenomenon of nonlytic exocytosis, also referred to as "vomocytosis" or phagosome extrusion/expulsion, which involves the escape of fungal cells from the phagocyte with the survival of both cell types. this phenomenon has been observed only in vitro using subjective and time-consuming microscopic techniques. in spite of recent advances in our knowledge about its mechanisms, a major question ...201121828219
antimicrobial sesquiterpenoids from laurus nobilis l.activity-guided fractionations of leaf extracts from laurus nobilis l. led to the isolation of a known sesquiterpene lactone, deacetyl laurenobiolide (1). compound 1 showed antimicrobial activity against periopathic pathogens (actinomyces viscosus, porphyromonas gingivalis, prevotella intermedia and actinobacillus actinomycetemcomitans), opportunistic gram-positive bacteria (staphylococcus aureus and streptococcus pyogenes) and fungi (candida albicans, cryptococcus neoformans and aspergillus fum ...201121678158
the homeostasis of iron, copper, and zinc in paracoccidioides brasiliensis, cryptococcus neoformans var. grubii, and cryptococcus gattii: a comparative analysis.iron, copper, and zinc are essential for all living organisms. moreover, the homeostasis of these metals is vital to microorganisms during pathogenic interactions with a host. most pathogens have developed specific mechanisms for the uptake of micronutrients from their hosts in order to counteract the low availability of essential ions in infected tissues. we report here an analysis of genes potentially involved in iron, copper, and zinc uptake and homeostasis in the fungal pathogens paracoccidi ...201121833306
eosinophils contribute to il-4 production and shape the t-helper cytokine profile and inflammatory response in pulmonary cryptococcosis.susceptibility to infection with cryptococcus neoformans is tightly determined by production of il-4. in this study, we investigated the time course of il-4 production and its innate cellular source in mice infected intranasally with c. neoformans. we show that pulmonary il-4 production starts surprisingly late after 6 weeks of infection. interestingly, in the lungs of infected mice, pulmonary t helper (th) cells and eosinophils produce significant amounts of il-4. in eosinophil-deficient +ödblg ...201121699881
invasion of cryptococcus neoformans into human brain microvascular endothelial cells is mediated through the lipid rafts-endocytic pathway via the dual specificity tyrosine-phosphorylation-regulated kinase 3 (dyrk3).cryptococcus neoformans is a neurotropic fungal pathogen, which provokes the onset of devastating meningoencephalitis. we used human brain microvascular endothelial cells (hbmec) as the in vitro model to investigate how c. neoformans traverses across the blood-brain barrier. in this report, we present several lines of evidence indicating that c. neoformans invasion is mediated through the endocytic pathway via lipid rafts. human cd44 molecules from lipid rafts can directly interact with hyaluron ...201121693704
characterisation of clinical isolates of the cryptococcus neoformans-c. gattii species complex from the amazonas state in brazil.background: the differentiation and classification of pathogenic cryptococcus species provides useful data for epidemiological studies and for the clinical diagnosis and treatment of patients. objectives: the aim of this study was to characterise 40 clinical cryptococcus obtained from patients at the tropical medicine foundation of amazonas (fmtam) from 2006 to 2008. methods: it was used phenotypic (i.e., enzyme production and antifungal resistance) and molecular biological (ura5-rflp) experimen ...201121699993
efficacy of intravenous amphotericin b-polybutylcyanoacrylate nanoparticles against cryptococcal meningitis in mice.amphotericin b deoxycholate (amb), a classic antifungal drug, remains the initial treatment of choice for deep fungal infections, but it is not appropriate for treatment of cryptococcal meningitis due to its inability to pass through the blood-brain barrier (bbb). we examined the efficacy of amphotericin b-polybutylcyanoacrylate nanoparticles (amb-pbca-nps) modified with polysorbate 80 that had a mean particle diameter less than 100 nanometers (69.0 -¦ 28.6 nm). amb-pbca-nps were detected in the ...201121720503
dynamics of cryptococcus neoformans-macrophage interactions reveal that fungal background influences outcome during cryptococcal meningoencephalitis in humans.abstract cryptococcosis is a multifaceted fungal infection with variable clinical presentation and outcome. as in many infectious diseases, this variability is commonly assigned to host factors. to investigate whether the diversity of cryptococcus neoformans clinical (clincn) isolates influences the interaction with host cells and the clinical outcome, we developed and validated new quantitative assays using flow cytometry and j774 macrophages. the phenotype of clincn-macrophage interactions was ...201121828220
Functional analysis of host factors that mediate the intracellular lifestyle of Cryptococcus neoformans.Cryptococcus neoformans (Cn), the major causative agent of human fungal meningoencephalitis, replicates within phagolysosomes of infected host cells. Despite more than a half-century of investigation into host-Cn interactions, host factors that mediate infection by this fungal pathogen remain obscure. Here, we describe the development of a system that employs Drosophila S2 cells and RNA interference (RNAi) to define and characterize Cn host factors. The system recapitulated salient aspects of fu ...201121698225
[Cryptococcal meningitis in children: description of 3 cases].Cryptococcal meningitis is much less common in children than adults. The purpose of this report is to describe 3 cases of cryptococcal meningitis observed in children admitted to the Neurology Department of the Fann University Hospital Center in Dakar, Senegal between July 2003 and November 2008. There were 2 girls whose ages were 8 and 15 years and one 9-year-old boy. All 3 patients presented acute or chronic meningoencephalitis. Diagnosis was based on direct microscopic examination of India in ...201121695878
role of phospholipases in fungal fitness, pathogenicity, and drug development - lessons from cryptococcus neoformans.many pathogenic microbes, including many fungi, produce phospholipases which facilitate survival of the pathogen in vivo, invasion and dissemination throughout the host, expression of virulence traits and evasion of host immune defense mechanisms. these phospholipases are either secreted or produced intracellularly and act by physically disrupting host membranes, and/or by affecting fungal cell signaling and production of immunomodulatory effectors. many of the secreted phospholipases acquire a ...201021687772
the c2 domain protein cts1 functions in the calcineurin signaling circuit during high-temperature stress responses in cryptococcus neoformans.calcineurin is a conserved calcium/calmodulin-dependent serine/threonine-specific protein phosphatase that acts in cell stress responses. calcineurin is essential for growth at 37°c and for virulence of the human fungal pathogen cryptococcus neoformans, but its substrates remain unknown. the c2 domain-containing, phospholipid-binding protein cts1 was previously identified as a multicopy suppressor of a calcineurin mutation in c. neoformans. here we further characterize the function of cts1 and t ...201122002655
cryptococcus neoformans isolation from swallow (hirundo rustica) excreta in iran.cryptococcus neoformans is an encapsulated yeast that can cause cryptococcosis, a life-threatening infection that mainly occurs in immunocompromised patients. the major environmental sources of c. neoformans have been shown to be soil contaminated with avian droppings. in the present study, we evaluated the isolation of c. neoformans from swallow (hirundo rustica) excreta in two northern cities of iran. ninety-seven swallow droppings were evaluated and 498 yeast-like colonies were isolated and i ...201121755233
prognostic markers in aids-related cryptococcal meningitis.despite the advent and expanding access to antiretroviral therapy, hiv-associated cryptococcal meningitis (cm) remains a significant cause of mortality and morbidity amongst individuals with this infection in resource-limited settings.201121751623
cryptococcus neoformans as a model for radioimmunotherapy of infections.there is an obvious and urgent need for novel approaches to treat infectious diseases. the use of monoclonal antibodies in therapy of infectious diseases is now experiencing renewed interest. during the last 5 years radioimmunotherapy (rit), a modality previously developed only for cancer treatment, has been successfully adapted for the treatment of experimental fungal, bacterial, and viral infections. as our model organism for studying the efficacy, mechanisms, potential toxicity, and radioresi ...201121747848
snf1/ampk protein kinase modulates cell wall integrity in the human pathogenic yeast cryptococcus neoformans.the snf1/ampk family of protein kinases is highly conserved among eukaryotes. our previous study showed that cryptococcus neoformans snf1 played critical roles in the production of virulence factors and virulence itself. in this paper, we report a novel function of snf1 in cell wall integrity.201121866697
heterozygosis and pathogenicity of cryptococcus neoformans ad-hybrid isolates.nineteen cryptococcus neoformans ad-hybrid isolates were investigated to assess whether hybrid genomic background could affect virulence in a mouse model. the level of heterozygosity of each strain was analyzed using primers specific for allele a and d of 15 polymorphic genes. virulence was tested in a mouse model of systemic infection by measuring time of survival. in addition, the putative virulence attributes, melanin, phospholipase, and capsule production, as well as growth at 39°c and uv se ...201121922248
association of calcineurin with the copi protein sec28 and the copii protein sec13 revealed by quantitative proteomics.calcineurin is a calcium-calmodulin-dependent serine/threonine specific protein phosphatase operating in key cellular processes governing responses to extracellular cues. calcineurin is essential for growth at high temperature and virulence of the human fungal pathogen cryptococcus neoformans but the underlying mechanism is unknown. we performed a mass spectrometry analysis to identify proteins that associate with the calcineurin a catalytic subunit (cna1) in c. neoformans cells grown under non- ...201121984910
Comparison of real-time florescence quantitative PCR measurements of VAD1 mRNA with three conventional methods in diagnosis and follow-up treatment of Cryptococcus neoformans infection.This study was to develop a real-time florescence quantitative PCR (RT-FQ-PCR) assay to measure virulence-associated DEAD-box RNA helicase (VAD1) mRNA from Cryptococcus neoformans and evaluate its potential use in diagnosis and follow-up treatment of C. neoformans meningitis (CNM). Cryptococcus neoformans was detected using RT-FQ-PCR, ink staining, fungal culturing and C. neoformans antigen detection in CNM compared with a normal control. VAD1 mRNA was measured in both acute and stable CNM patie ...201121895785
eosinophils elicit proliferation of naive and fungal-specific cells in vivo so enhancing a t helper type 1 cytokine profile in favour of a protective immune response against cryptococcus neoformans infection.experimental cryptococcus neoformans infection in rats has been shown to have similarities with human cryptococcosis, because as in healthy humans, rats can effectively contain cryptococcal infection. moreover, it has been shown that eosinophils are components of the immune response to c. neoformans infections. in a previous in vitro study, we demonstrated that rat peritoneal eosinophils phagocytose opsonized live yeasts of c. neoformans, thereby triggering their activation, as indicated by the ...201121896014
Treatment of Early and Established Cryptococcus neoformans Infection with Radiolabeled Antibodies in Immunocompetent Mice.We investigated the utility of radioimmunotherapy (RIT) in early and established cryptococcal infection in immunocompetent mice. RIT with (213)Bi-18B7 antibody completely eliminated fungus from mouse lungs and brains for early infection, while (188)Re-18B7 significantly reduced CFU in the lungs or both lungs and brains during early and established infection, respectively. The results point to the independence of RIT of the immune status of the host, which is encouraging for translation of this s ...201222005995
Are all psittacine birds carriers of Cryptococcus neoformans? 201122012238
ten challenges on cryptococcus and cryptococcosis.cryptococcosis has become a significant public global health problem worldwide. caused by two species, cryptococcus neoformans or cryptococcus gattii, this life-threatening infection afflicts not only immunocompromised individuals but also apparently immunocompetent subjects. hence, cryptococcosis should no longer be considered merely an opportunistic infection. in this article, we focus on ten unanswered questions/topics in this field with the hope to stimulate discussion and research on these ...201121948062
interaction of triosephosphate isomerase from staphylococcus aureus with plasminogen.triosephosphate isomerase (tpi; ec 5. 3. 1. 1) displayed on the cell surface of staphylococcus aureus acts as an adhesion molecule that binds to the capsule of cryptococcus neoformans, a fungal pathogen. this study investigated the function of tpi on the cell surface of s. aureus and its interactions with biological substances such as fibronectin, fibrinogen, plasminogen, and thrombin were investigated. binding of tpi to plasminogen was demonstrated by both surface plasmon resonance analysis and ...201122003920
Towards understanding cell cycle control in Cryptococcus neoformans: Structure-function relationship of G1 and G1/S cyclins homologue CnCln1.We have previously reported that only a single Cdk1-related G1 and G1/S cyclin homologue was found in the genome sequence of the pathogenic basidiomycetous yeast Cryptococcus neoformans (C. neoformans) and designated it CnCln1. Surprisingly, CnCln1 was not only able to complement the function of the G1 cyclins of the ascomycetous budding yeast Saccharomyces cerevisiae (S. cerevisiae), such as ScCln3, but also the G1/S cyclins of S. cerevisiae, such as ScCln1 and ScCln2. In this study, we investi ...201122119191
Effects of microplusin, a copper-chelating antimicrobial peptide, against Cryptococcus neoformans.Microplusin is an antimicrobial peptide isolated from the cattle tick Rhipicephalus (Boophilus) microplus. Its copper-chelating ability is putatively responsible for its bacteriostatic activity against Micrococcus luteus as microplusin inhibits respiration in this species, which is a copper-dependent process. Microplusin is also active against Cryptococcus neoformans (MIC(50) = 0.09 µM), the etiologic agent of cryptococcosis. Here, we show that microplusin is fungistatic to C. neoformans and thi ...201122092765
Requirement of a Tsp2-Type Tetraspanin for Laccase Repression and Stress Resistance in the Basidiomycete Cryptococcus neoformans.Fungal laccases have been widely used in industry. The expression of laccase often is repressible by the primary carbon source glucose in many fungi. The underlying basis is largely unclear. We demonstrate here that a gene, TSP2-1, was required for laccase repression by glucose in the basidiomycete Cryptococcus neoformans. TSP2-1 encodes a Tsp2-type tetraspanin. The disruption of TSP2-1 resulted in constant melanin formation and the expression of the laccase gene LAC1. This derepression phenotyp ...201222020508
toward developing a universal treatment for fungal disease using radioimmunotherapy targeting common fungal antigens.background: previously, we demonstrated the ability of radiolabeled antibodies recognizing the cryptococcal polysaccharide capsule to kill cryptococcus neoformans both in vitro and in infected mice. this approach, known as radioimmunotherapy (rit), uses the exquisite ability of antibodies to bind antigens to deliver microbicidal radiation. to create rit reagents which would be efficacious against all major medically important fungi, we have selected monoclonal antibodies (m ...201122048869
Deletion of Cryptococcus neoformans AIF Ortholog Promotes Chromosome Aneuploidy and Fluconazole-Resistance in a Metacaspase-Independent Manner.Apoptosis is a form of programmed cell death critical for development and homeostasis in multicellular organisms. Apoptosis-like cell death (ALCD) has been described in several fungi, including the opportunistic human pathogen Cryptococcus neoformans. In addition, capsular polysaccharides of C. neoformans are known to induce apoptosis in host immune cells, thereby contributing to its virulence. Our goals were to characterize the apoptotic signaling cascade in C. neoformans as well as its unique ...201122114551
Protection of melanized Cryptococcus neoformans from lethal dose gamma irradiation involves changes in melanin's chemical structure and paramagnetism.Certain fungi thrive in highly radioactive environments including the defunct Chernobyl nuclear reactor. Cryptococcus neoformans (C. neoformans), which uses L-3,4-dihydroxyphenylalanine (L-DOPA) to produce melanin, was used here to investigate how gamma radiation under aqueous aerobic conditions affects the properties of melanin, with the aim of gaining insight into its radioprotective role. Exposure of melanized fungal cell in aqueous suspensions to doses of ?-radiation capable of killing 50 to ...201121966422
adalimumab-associated pulmonary cryptococcosis.this is the first report of adalimumab-associated pulmonary cryptococcosis. a 56-year-old female with rheumatoid arthritis without a history of pulmonary disease was simultaneously administered adalimumab (40 mg/2 wks), methotrexate (4 mg/wk), and isoniazid (200 mg/day). five months later, chest radiography revealed a small spiculated pulmonary nodule, and the laboratory test results, including levels of tumor markers and plasma β-d-glucan, were within normal ranges. since the lesion continued t ...201121881327
genotypes of cryptococcus neoformans and cryptococcus gattii as agents of endemic cryptococcosis in teresina, piauí (northeastern brazil).throughout brazil, cryptococcus neoformans is the cause of cryptococcosis, whereas cryptococcus gattii is endemic to the northern and northeastern states. in this study, the molecular types of 63 cryptococcal isolates recovered from the cerebrospinal fluid of meningitis patients diagnosed between 2008-2010 in teresina, piauí, brazil, were analysed. out of the 63 patients, 37 (58.7%) were human immunodeficiency virus (hiv)-positive and 26 (41.3%) were hiv-negative. ura5-restriction fragment lengt ...201122012227
'Popping the Clutch': Novel Mechanisms Regulating Sexual Development in Cryptococcus neoformans.Sexual reproduction in fungal pathogens such as Cryptococcus provides natural selection and adaptation of the organisms to environmental conditions by allowing beneficial mutations to spread. However, successful mating in these fungi requires a time-critical induction of signaling pheromones when appropriate partners become available. Recently, it has been shown that the fungus uses the transcriptional equivalent of the racing technique: 'popping the clutch'-pushing in the clutch pedal, putting ...201121912854
therapeutic drug monitoring of voriconazole in children.voriconazole is an extended-spectrum triazole antifungal with activity against a wide variety of pathogens, including aspergillus, candida, cryptococcus neoformans, fusarium, and scedosporium. it exerts its antifungal activity by blocking the synthesis of fungal cell membranes and is considered the first-line treatment for invasive aspergillosis. because the pharmacokinetics of voriconazole can demonstrate considerable variability, it has been suggested that monitoring plasma levels of voriconaz ...201122210097
cryptococcus neoformans ca(2+) homeostasis requires a chloride channel/antiporter clc1 in jec21, but not in h99.clc-type chloride/proton antiporters are required for copper/iron homeostasis in fungi. a relationship between clcs and ca(2+) homeostasis has not been found before. here we demonstrate the requirement of the antiporter clc1 for ca(2+) homeostasis/signaling in cryptococcus neoformans. the deletion of clc1 in jec21 resulted in a mutant hypersensitive to cyclosporine a, an inhibitor of calcineurin. intracellular ca(2+) deficiency in the mutant tx1 was confirmed with fluo-3 staining epi-fluoresc ...201122093100
diagnostic value of latex agglutination in cryptococcal meningitis.cryptococcus neoformans is the most common fungal pathogen to infect the central nervous system, and an effective diagnostic method is therefore necessary for the early diagnosis of cryptococcal meningitis.200921938253
toward an integrated model of capsule regulation in cryptococcus neoformans.cryptococcus neoformans is an opportunistic fungal pathogen that causes serious human disease in immunocompromised populations. its polysaccharide capsule is a key virulence factor which is regulated in response to growth conditions, becoming enlarged in the context of infection. we used microarray analysis of cells stimulated to form capsule over a range of growth conditions to identify a transcriptional signature associated with capsule enlargement. the signature contains 880 genes, is enriche ...201122174677
quantitative evaluation of cryptococcal pathogenesis and antifungal drugs using a silkworm infection model with cryptococcus neoformans.to develop an in vivo system that could quantitatively evaluate the therapeutic effects of antifungal drugs using a silkworm infection model with cryptococcus neoformans.201222040451
Magnetic Resonance Spectroscopy Findings of Pyogenic, Tuberculous, and Cryptococcus Intracranial Abscesses.Proton magnetic resonance spectroscopy (MRS) complements conventional methods used to differentiate intracranial cystic lesions. We report MRS findings of three cases that were diagnosed as pyogenic, tuberculous, and Cryptococcus abscesses before instituting any medical or surgical therapy. The pyogenic brain abscess had typical specific spectral findings (i.e., the demonstration of amino acids). Lactate and lipid peaks were visible in the tuberculous abscess. Cryptococcus neoformans can appear ...201122002661
Inhibition of HIV entry by extracellular glucuronoxylomannan of Cryptococcus neoformans.Cryptococcosis, caused by Cryptococcus neoformans, is the most common opportunistic fungal disease in HIV/AIDS patients. The prognosis of AIDS patients with Cryptococcus infection is very poor. One of the major characteristics in cryptococcosis patients is the presence of high concentrations of the cryptococcal capsule polysaccharide (CCP) in the serum and cerebrospinal fluid. CCP enhances HIV replication in H9 T-cells, but the mechanism is unknown. In this study, we tested whether extracellular ...201221983597
Dithiocarbamates are strong inhibitors of the beta-class fungal carbonic anhydrases from Cryptococcus neoformans, Candida albicans and Candida glabrata.A series of N-mono- and N,N-disubstituted dithiocarbamates have been investigated as inhibitors of three ß-carbonic anhydrases (CAs, EC 4.2.1.1) from the fungal pathogens Cryptococcus neoformans, Candida albicans and Candida glabrata, that is, Can2, CaNce103 and CgNce103, respectively. These enzymes were inhibited with efficacies between the subnanomolar to the micromolar range, depending on the substitution pattern at the nitrogen atom from the dithiocarbamate zinc-binding group. This new class ...201122209456
Development of specific SCAR markers for detecting Histoplasma capsulatum in clinical and environmental samples.Sequence-characterized amplified region (SCAR) markers, generated by randomly amplified polymorphic DNA (RAPD)-PCR, were developed to detect Histoplasma capsulatum selectively in clinical and environmental samples. A 1200-bp RAPD-PCR-specific band produced with the 1281-1283 primers was cloned, sequenced, and used to design two SCAR markers, 1281-1283(220) and 1281-1283(230). The specificity of these markers was confirmed by Southern hybridization. To evaluate the relevance of the SCAR markers f ...201122189121
Emerging themes in cryptococcal capsule synthesis.Cryptococcus neoformans, a basidiomycete yeast and opportunistic pathogen, expends significant biosynthetic effort on construction of a polysaccharide capsule with a radius that may be many times that of the cell. Beyond posing a stimulating challenge in terms of defining biosynthetic pathways, the capsule is required for this yeast to cause fatal disease. This combination has focused the attention of researchers on this system. Here we briefly review two aspects of the rapidly advancing field o ...201121889889
proanthocyanidin-rich extracts from cranberry fruit ( vaccinium macrocarpon ait.) selectively inhibit the growth of human pathogenic fungi candida spp. and cryptococcus neoformans.cranberry ( vaccinium macrocarpon ) has been shown in clinical studies to reduce infections caused by escherichia coli and other bacteria, and proanthocyanidins are believed to play a role. the ability of cranberry to inhibit the growth of opportunistic human fungal pathogens that cause oral, skin, respiratory, and systemic infections has not been well-studied. fractions from whole cranberry fruit were screened for inhibition of five candida species and cryptococcus neoformans , a causative ...201122066866
Variation in chromosome copy number influences the virulence of Cryptococcus neoformans and occurs in isolates from AIDS patients.The adaptation of pathogenic fungi to the host environment via large-scale genomic changes is a poorly characterized phenomenon. Cryptococcus neoformans is the leading cause of fungal meningoencephalitis in HIV/AIDS patients, and we recently discovered clinical strains of the fungus that are disomic for chromosome 13. Here, we examined the genome plasticity and phenotypes of monosomic and disomic strains, and compared their virulence in a mouse model of cryptococcosis201122032296
srebp coordinates iron and ergosterol homeostasis to mediate triazole drug and hypoxia responses in the human fungal pathogen aspergillus fumigatus.sterol regulatory element binding proteins (srebps) are a class of basic helix-loop-helix transcription factors that regulate diverse cellular responses in eukaryotes. adding to the recognized importance of srebps in human health, srebps in the human fungal pathogens cryptococcus neoformans and aspergillus fumigatus are required for fungal virulence and susceptibility to triazole antifungal drugs. to date, the exact mechanism(s) behind the role of srebp in these observed phenotypes is not clear. ...201122144905
structural analysis of fungal cerebrosides.of the ceramide monohexosides (cmhs), gluco- and galactosyl-ceramides are the main neutral glycosphingolipids expressed in fungal cells. their structural determination is greatly dependent on the use of mass spectrometric techniques, including fast atom bombardment-mass spectrometry, electrospray ionization, and energy collision-induced dissociation mass spectrometry. nuclear magnetic resonance has also been used successfully. such a combination of techniques, combined with classical analytical ...201122164155
Clinico-radiological features of subarachnoid hyperintensity on diffusion-weighted images in patients with meningitis.AIM: To investigate the clinical and radiological features of meningitis with subarachnoid diffusion-weighted imaging (DWI) hyperintensity. MATERIALS AND METHODS: The clinical features, laboratory data, and radiological findings, including the number and distribution of subarachnoid DWI hyperintense lesions and other radiological abnormalities, of 18 patients seen at five institutions were evaluated. RESULTS: The patients consisted of eight males and 10 females, whose ages ranged from 4 months t ...201122192625
cryptococcus gattii: a resurgent fungal pathogen.cryptococcus gattii and cryptococcus neoformans are causal agents of cryptococcosis, which manifests as pneumonia and meningitis. c. gattii has recently received widespread attention owing to outbreaks in british columbia, canada and the us pacific northwest. the biology of this tree-dwelling yeast is relatively unexplored, and there are few clues about how it causes infections in humans and animals. in this review, we summarize recent discoveries about c. gattii genetics and its ecological nich ...201121880492
The decline of typhoid and the rise of non-typhoid salmonellae and fungal infections in a changing HIV landscape: bloodstream infection trends over 15 years in southern Vietnam.The etiological spectrum of bloodstream infections is variable between industrialized and developing countries and even within a defined location over time. We investigated trends in bloodstream infections at an infectious disease hospital in Ho Chi Minh City, Vietnam, from 1994-2008. Amongst 66111 blood cultures performed, a clinically relevant pathogen was isolated in 7645 episodes (positivity rate; 116/1000 cultures). Salmonella Typhi was the predominant pathogen until 2002; however, a consid ...201222137537
isolation of the volatile oil from satureja thymbra by supercritical carbon dioxide extraction: chemical composition and biological activity.satureja thymbra l. is well known in italy by the popular name of "santoreggia sarda". it grows only in sardinia and nowadays it is restricted to the slope of the colle san michele in cagliari. the composition of the aromatic extracts obtained by supercritical co2 and by hydrodistillation and their antifungal activity is reported. the collected extracts were analyzed by gc-fid and gc-ms methods. no significant differences were observed in the composition of the volatile extracts depending on the ...201122164799
a flucytosine-responsive mbp1/swi4-like protein, mbs1, plays pleiotropic roles in antifungal drug resistance, stress response, and virulence of cryptococcus neoformans.cryptococcosis, caused by the basidiomycetous fungus cryptococcus neoformans, is responsible for more than 600,000 deaths annually in aids patients. flucytosine is one of the most commonly used antifungal drugs for its treatment, but its resistance and regulatory mechanisms have never been investigated at the genome scale in c. neoformans. in the present study, we performed comparative transcriptome analysis by employing two-component system mutants (tco1δ and tco2δ) exhibiting opposing flucytos ...201222080454
toll-like receptor 9 modulates macrophage antifungal effector function during innate recognition of candida albicans and saccharomyces cerevisiae.phagocytic responses are critical for effective host defense against opportunistic fungal pathogens. macrophages sample the phagosomal content and orchestrate the innate immune response. toll-like receptor 9 (tlr9) recognizes unmethylated cpg dna and is activated by fungal dna. here we demonstrate that specific triggering of tlr9 recruitment to the macrophage phagosomal membrane is a conserved feature of fungi of distinct phylogenetic origins, including candida albicans, saccharomyces cerevisiae ...201121947771
[primary cutaneous cryptococcosis in a pigeon breeder].a danish 73 year-old male patient with polymyalgia rheumatica and in prednisone treatment presented with a cutaneous ulcer on the hand caused by a scratch from a pigeon. initial treatment with antibiotics was unsuccessful. biopsy revealed cryptococcus neoformans and the patient recovered on antifungal treatment. primary cutaneous cryptococcosis is a rare manifestation of a c. neoformans infection. this case exemplifies the importance of differential diagnosis in immunosuppressed patients who do ...201121958488
chronological aging is associated with biophysical and chemical changes in the capsule of cryptococcus neoformans.does the age of a microbial cell affect its virulence factors? to our knowledge, this question has not been addressed previously, but the answer is of great relevance for chronic infections where microbial cells persist and age in hosts. cryptococcus neoformans is an encapsulated human-pathogenic fungus notorious for causing chronic infections where cells of variable age persist in tissue. the major virulence factor for c. neoformans is a polysaccharide (ps) capsule. to understand how chronologi ...201121968999
post-translational modifications of proteins in the pathobiology of medically relevant fungi.post-translational modifications of proteins drive a wide variety of cellular processes in eukaryotes, regulating cell growth and division as well as adaptive and developmental processes. with regard to the fungal kingdom, most information about post-translational modifications has been generated through studies of the model yeasts saccharomyces cerevisiae and schizosaccharomyces pombe, where for example, the roles of protein phosphorylation, glycosylation, acetylation, ubiquitination, sumoylati ...201122158711
cryptococcus neoformans modulates extracellular killing by neutrophils.we recently established a key role for host sphingomyelin synthase (sms) in regulating the killing activity of neutrophils against cryptococcus neoformans. in this paper, we studied the effect of c. neoformans on the killing activity of neutrophils and whether sms would still be a player against c. neoformans in immunocompromised mice lacking t and natural killer (nk) cells (tgε26 mice). to this end, we analyzed whether c. neoformans would have any effect on neutrophil survival and killing in vi ...201121960987
bovine cryptococcal meningoencephalitis.cryptococcal meningitis and encephalitis is reported in a 5-year-old bull. the clinical signs included multifocal neurological deficits manifested by hypermetria, ataxia, depression, circling, impaired vision, head pressing, low head carriage, wide-based stance, and falling to the side or backwards. at necropsy, 6 cavities with a gelatinous content were observed in the brain and brain stem, and the meninges were thickened and off white. numerous yeasts, with a nonstaining capsule, and associated ...201121908375
synthesis and antifungal activity of 6,7-bis(arylthio)-quinazoline-5,8-diones and furo[2,3-f]quinazolin-5-ols.6,7-bis(arylthio)-quinazoline-5,8-dione and furo[2,3-f]quinazolin-5-ol derivatives were synthesized and tested for in vitro antifungal activity against candida, aspergillus species, and cryptococcus neoformans. among them tested, many of furo[2,3-f]quinazolin-5-ols and 6,7-bis(arylthio)-quinazoline-5,8-diones showed good antifungal activity. the compounds 4a and 4e completely inhibited the growth of all against candida and aspergillus species tested at the mic level of 12.5μg/ml. the results sug ...201222113112
correlation of susceptibility of cryptococcus neoformans to amphotericin b with clinical outcome.testing of cryptococcus neoformans for susceptibility to antifungal drugs by standard microtiter methods has not been shown to correlate with clinical outcomes. this report describes a modified quantitative broth macrodilution susceptibility method showing a correlation with both the patient's quantitative biological response in the cerebrospinal fluid (csf) and the survival of 85 patients treated with amphotericin b (amb). the spearman rank correlation between the quantitative in vitro measure ...201121947402
detection of yeasts in blood cultures by the luminex xtag fungal assay.a multiplex-pcr luminex xmap bead probe fluid array using xtag analyte-specific reagents (multiplex xtag fungal asr assay) was employed for detection of clinically significant candida species, cryptococcus neoformans, histoplasma capsulatum, and blastomyces dermatitidis from blood cultures. we tested 132 blood cultures negative (n = 10) or positive (n = 97) for yeasts and/or bacteria (n = 25). the assay showed sensitivity and specificity of 100% and 99%, respectively. the xtag fungal asr assay i ...201122170902
biophysical methods for the study of microbial surfaces.the challenge in studying the surface architecture of different microbial pathogens is to integrate the most current biochemical, spectroscopic, microscopic, and processing techniques. individually these methods have insufficient sensitivity to reveal complex structures, such as branched, large, viscous polymers with a high structure hydration, size, and complexity. however, when used in combination biophysical techniques are our primary source of information for understanding polydisperse molec ...201122013430
adaptation of cryptococcus neoformans to mammalian hosts: integrated regulation of metabolism and virulence.the basidiomycete fungus, cryptococcus neoformans, infects humans via inhalation of desiccated yeast cells or spores from the environment. in the absence of effective immune containment, the initial pulmonary infection often spreads to the central nervous system to result in meningoencephalitis. the fungus must therefore make the transition from the environment to different mammalian niches that include the intracellular locale of phagocytic cells and extracellular sites in the lung, bloodstream ...201122140231
in vitro antifungal activity of dna topoisomerase inhibitors.in this paper we report the results of the study of the in vitro effect of eight anticancer dna topoisomerase inhibitors on the growth of aspergillus fumigatus, a. niger, candida glabrata and cryptococcus neoformans. only one compound, idarubicin, displayed promising antifungal activity against a. niger, c. glabrata and c. neoformans with mic(50) values varying between 3.6 and 14.2 μm (1.8-7.1 μg/ml). three other compounds, aclarubicin, doxorubicin and mitoxantrone, showed some antifungal activi ...201121939347
the synthesis of xanthones, xanthenediones, and spirobenzofurans: their antibacterial and antifungal activity.exposure of the phenol, (5-bromo-2-hydroxyphenyl)(2,4,5-trimethoxyphenyl)methanone 18 to ceric ammonium nitrate (can) resulted in the formation of 7-bromo-3,4a-dimethoxy-2h-xanthene-2,9(4ah)-dione 19 and 5-bromo-2',5'-dimethoxy-3h-spiro[benzofuran-2,1'-cyclohexa[2,5]diene]-3,4'-dione 20. the brominated spirobenzofuran 20 was then subjected to suzuki-miyaura reactions to give six derivatives 22a-f. these compounds, related diones and xanthones displayed mostly noteworthy antimicrobial activity, p ...201122014830
evaluation of the detection of melanin by the fontana-masson silver stain in tissue with a wide range of organisms including cryptococcus.it is not uncommon for surgical pathologists to encounter yeast and yeast-like organisms in tissue sections, and correct identification is imperative for guiding therapy. the fontana-masson silver stain for detecting melanin has been accepted as a relatively specific stain for diagnosing cryptococcosis in tissue based on few studies with limited numbers of organisms. this study was designed to test the value of the fontana-masson silver by investigating a large collection of tissues with infecti ...201122154051
methylxanthine inhibit fungal chitinases and exhibit antifungal activity.chitinases are necessary for fungal cell wall remodeling and cell replication. methylxanthines have been shown to competitively inhibit family 18 chitinases in vitro. we sought to determine the effects of methylxanthines on fungal chitinases. fungi demonstrated variable chitinase activity and incubation with methylxanthines (0.5-10 mm) resulted in a dose-dependent decrease in this activity. all fungi tested, except for candida spp., demonstrated growth inhibition in the presence of methylxanthin ...201121968902
wild-type mic distributions and epidemiologic cutoff values for fluconazole, posaconazole, and voriconazole when testing cryptococcus neoformans as determined by the clsi broth microdilution method.when clinical susceptibility breakpoints (cbps) are absent, establishing wild-type (wt) mic distributions and epidemiologic cutoff values (ecvs) provides a sensitive means for detecting emerging resistance to antimicrobials. we determined species-specific ecvs for fluconazole (flc), posaconazole (psc), and voriconazole (vrc) using a large global collection of cryptococcus neoformans (cneo) isolates obtained from the artemis and sentry antimicrobial surveillance programs. from 2006 to 2009, 285 i ...201121917395
induction of protective immunity against cryptococcosis.cryptococcus neoformans, the predominant etiological agent of cryptococcosis, is an encapsulated fungal pathogen that can cause life-threatening infections of the central nervous system in immune compromised individuals resulting in high morbidity and mortality. consequently, several studies have endeavored to understand those mechanisms that mediate resistance and susceptibility to cryptococcus infection. in this review, we will examine the contributions of various components of the innate and ...201122143898
cryptococcus neoformans suppresses the activation of bone marrow-derived dendritic cells stimulated with its own dna, but not with dna from other fungi.dna from cryptococcus neoformans activates bone marrow-derived dendritic cells (bm-dcs) in a tlr9-dependent manner. in this study, we examined the effect of the culture supernatants of c. neoformans on the activation of bm-dcs caused by its own dna. c. neoformans supernatants suppressed il-12p40, il-6 production and cd40 expression by bm-dcs stimulated with its own dna, but not with cpg-odn and dna from candida albicans, saccharomyces cerevisiae or escherichia coli. in a confocal microscopic ana ...201122092563
Quality Control of Fungus-specific Glucosylceramide in Cryptococcus neoformans by Endoglycoceramidase-related Protein 1 (EGCrP1).A fungus-specific glucosylceramide (GlcCer), which contains a unique sphingoid base possessing two double bonds and a methyl substitution, is essential for pathogenicity in fungi. Although the biosynthetic pathway of the GlcCer has been well elucidated, little is known about GlcCer catabolism because a GlcCer-degrading enzyme (glucocerebrosidase) has yet to be identified in fungi. We found a homologue of endoglycoceramidase tentatively designated endoglycoceramidase-related protein 1 (EGCrP1) in ...201222072709
clinical, epidemiological and outcome features of patients with cryptococcosis in uberaba, minas gerais, brazil.nearly one million of cryptococcosis cases occur yearly around the world, involving mainly hiv-infected patients who are not receiving antiretroviral therapy (art) or present poor adherence. this study aims to evaluate epidemiological, clinical and outcome aspects of patients with cryptococcosis from 1998-2010. patients were prospectively recruited, and their medical and laboratory records were reviewed. a total of 131 cases were included, and of these, 119 (90.83%) had aids, 4 received a renal ...201122130645
synthesis, stereochemistry and in vitro antimicrobial evaluation of novel 2-[(2,4-diaryl-3-azabicyclo[3.3.1]nonan-9-ylidene)hydrazono]-4-phenyl-2,3-dihydrothiazoles.2-[(2,4-diaryl-3-azabicyclo[3.3.1]nonan-9-ylidene)hydrazono]-4-phenyl-2,3-dihydrothiazoles (3a-3k) have been synthesized by the cyclization of 2-[(2,4-diaryl-3-azabicyclo[3.3.1]nonan-9-one thiosemicarbazones with phenacyl bromide and characterized by analytical (melting point and elemental analysis) and spectral (ir, (1)h nmr, (13)c nmr, d(2)o exchange, noesy and mass) techniques. the novel hantzsch products (3a-3k) were screened for their in vitro antibacterial and antifungal activities against ...201121958543
pseudomonas aeruginosa inhibits the growth of cryptococcus species.pseudomonas aeruginosa is a ubiquitous and opportunistic bacterium that inhibits the growth of different microorganisms, including gram-positive bacteria and fungi such as candida spp. and aspergillus fumigatus. in this study, we investigated the interaction between p. aeruginosa and cryptococcus spp. we found that p. aeruginosa pa14 and, to a lesser extent, pao1 significantly inhibited the growth of cryptococcus spp. the inhibition of growth was observed on solid medium by the visualization of ...201122076410
Blood-brain barrier invasion by Cryptococcus neoformans is enhanced by functional interactions with plasmin.Cryptococcus neoformans can invade the central nervous system through diverse mechanisms. We examined a possible role for host plasma proteases in the neurotropic behaviour of this blood-borne fungal pathogen. Plasminogen is a plasma-enriched zymogen that can passively coat the surface of blood-borne pathogens and, upon conversion to the serine protease plasmin, facilitate pathogen dissemination by degrading vascular barriers. In this study, plasminogen-to-plasmin conversion on killed and viable ...201221998162
influence of caspule size on the in vitro activity of antifungal agents against clinical cryptococcus neoformans variety grubii strains.cryptococcosis cause disseminated disease in aids patients. in contrast to what occurs in laboratory conditions, a large capsule is produced by c. neoformans in vivo during infection. aim: to compare the in vitro activity of different antifungal agents against 34 clinical isolates of cryptococcus neoformans var. grubii with or without capsule induction (clsi, clsi-c) following the clsi m27a3 document. capsule induction was obtained by addition of nahco(3) and incubation with co(2). results: ...201122074850
sodium butyrate inhibits pathogenic yeast growth and enhances the functions of macrophages.butyrate is a short-chain fatty acid that is produced by several human commensal bacteria, such as clostridium and lactobacillus species. butyrate is also known to inhibit histone deacetylase. in this study we assessed the antifungal activity of sodium butyrate (sb) against the human pathogenic yeasts candida albicans, candida parapsilosis and cryptococcus neoformans.201121911344
increased chitinase expression and fungal-specific antibodies in the bronchoalveolar lavage fluid of asthmatic children.background: increasing evidence highlights the contribution of chitinases and fungal infection to the development of asthma. objective: the purpose of this study was to characterize chitinase expression and serological markers of fungal infection in children with severe asthma. methods: bronchoalveolar lavage fluid (balf) was collected from children undergoing clinically indicated flexible bronchoscopy. a diagnosis of asthma was confirmed by pulmonary function testing. balf was tested for chitin ...201122092749
in vitro photodynamic inactivation of cryptococcus neoformans melanized cells with chloroaluminum phthalocyanine nanoemulsion.the selection of fungi resistant to currently used fungicides and the emergence of new pathogenic species make the development of alternative fungus-control techniques highly desirable. photodynamic antimicrobial chemotherapy (pact) is a promising method which combines a nontoxic photosensitizer (ps) with visible light to cause selective killing of microbial cells. the development of pact to treat mycoses or kill fungi in the environment depends on identifying effective ps for the different path ...201122145636
correlation of antifungal susceptibility and molecular type within the cryptococcus neoformans/c. gattii species complex.members of the cryptococcus neoformans/c. gattii species complex are grouped into eight molecular types, differing in their epidemiology, disease severity and geographic range. recent in vitro antifungal susceptibility studies of isolates of the complex revealed contradictory results. the objective of the present study was to assess if this variation is random or correlates with different molecular types by testing the in vitro antifungal susceptibility of 18 c. neoformans (vni), 11 c. gattii (v ...201121859388
paradoxical roles of alveolar macrophages in the host response to cryptococcus neoformans.cryptococcus neoformans (cn) is a fungal pathogen that is a serious health threat to immunocompromised individuals. upon environmental exposure, infectious fungal propagules are inhaled into the host's lungs. the anticryptococcal actions of alveolar macrophages (am), the predominant host phagocyte of the innate immune system in the lungs, are fundamental in determining whether containment and clearance of the pathogen occurs by the development of an adapted immune response or whether infection i ...201122045161
development of non-natural flavanones as antimicrobial agents.with growing concerns over multidrug resistance microorganisms, particularly strains of bacteria and fungi, evolving to become resistant to the antimicrobial agents used against them, the identification of new molecular targets becomes paramount for novel treatment options. recently, the use of new treatments containing multiple active ingredients has been shown to increase the effectiveness of existing molecules for some infections, often with these added compounds enabling the transport of a t ...201122039419
Chemical composition and biological activity of the volatile extracts of Achillea millefolium.In this study, flowering aerial parts of wild Achillea millefolium growing on the Mediterranean coast (Sardinia Island, Italy) and on the Atlantic coast (Portugal- Serra de Montemuro) were used as a matrix for supercritical extraction of volatile oil with CO2 (SFE). The collected extracts were analyzed by GC-FID and GC-MS methods and their composition were compared with that of the essential oil isolated by hydrodistillation. A strong chemical variability in essential oils depending on the origi ...201122164800
Amoeba provide insight into the origin of virulence in pathogenic fungi.Why are some fungi pathogenic while the majority poses no threat to humans or other hosts? Of the more than 1.5 million fungal species only about 150-300 are pathogenic for humans, and of these, only 10-15 are relatively common pathogens. In contrast, fungi are major pathogens for plants and insects. These facts pose several fundamental questions including the mechanisms responsible for the origin of virulence among the few pathogenic species and the high resistance of mammals to fungal diseases ...201222127880
identification of a cryptococcus neoformans cytochrome p450 lanosterol 14α-demethylase (erg11) residue critical for differential susceptibility between fluconazole/voriconazole and itraconazole/posaconazole.cryptococcus neoformans strains resistant to azoles due to mutations causing alterations in the erg11 gene, encoding lanosterol 14α-demethylase, have rarely been reported. in this study, we have characterized a c. neoformans serotype a strain that is resistant to high concentrations of fluconazole (flc). this strain which was isolated from a flc treated patient contained five missense mutations in the erg11 gene as compared to the reference strain h99. molecular manipulations of the erg11 gene c ...201122155829
methylation of glycosylated sphingolipid modulates membrane lipid topography and pathogenicity of cryptococcus neoformans.in previous studies we showed that the replication of cryptococcus neoformans in the lung environment is controlled by the glucosylceramide (glccer) synthase gene (gcs1), which synthesizes the membrane sphingolipid glccer from the c9-methyl ceramide. here, we studied the effect of the mutation of the sphingolipid c9 methyltransferase gene (smt1), which adds a methyl group to position 9 of the sphingosine backbone of ceramide. the c. neoformansδsmt1 mutant does not make c9-methyl ceramide and, th ...201122151739
[Pleiotropic drug resistance ABC transporters in fungi].Overexpression of pleiotropic drug resistance (PDR) efflux pumps of the ATP-binding cassette (ABC) transporter superfamily is the major cause of fungal multi-drug resistance and decreased efficacy of antifungal drugs. This review focused on recent progresses in understanding of the PDR efflux pumps of ABC transporter superfamily in Saccharomyces cerevisiae and the fungal pathogens Candida albicans, Cryptococcus neoformans, and Aspergillus fumigates. The mechanisms underlying efflux pump-mediated ...201121993279
long-term surveillance and treatment of subclinical cryptococcosis and nasal colonization by cryptococcus neoformans and c. gattii species complex in captive koalas (phascolarctes cinereus).cryptococcosis is an important systemic mycosis caused by members of the cryptococcus neoformans species complex. this disease is potentially fatal in various animals, including koalas. we describe the long-term surveillance and treatment of subclinical cryptococcosis and nasal colonization of koalas by cryptococcus neoformans and c. gattii. of the 15 animals investigated through the use of samples obtained by nasal swabs, antigen titer measurements, and pathologic examination, c. neoformans was ...201121859391
Curtains.A 55-year-old immunocompetent man presented with headache, nausea, progressive bilateral upper lid ptosis, and diplopia. Examination showed bilateral asymmetric upper lid ptosis with limited adduction and elevation of both eyes. Cranial magnetic resonance imaging revealed enhancing intra-axial and extra-axial midbrain lesions. Blood and cerebrospinal fluid were positive for cryptococcal antigen and cerebrospinal fluid fungal cultures grew Cryptococcus neoformans. Treatment with liposomal amphote ...201121855953
fulminant intracranial hypertension due to cryptococcal meningitis in a child with nephrotic syndrome.cryptococcus neoformans has a worldwide distribution. meningoencephalitis is the most common manifestation of cryptococcosis. the outcome of a patient with cryptococcal infection depends on the immune status of the host. patients with nephrotic syndrome are particularly susceptible to cryptococcal infection not only due to innate changes in their immune system but also because of the immunosuppressive agents used in the treatment. we report an 8-year-old boy with nephrotic syndrome, who develope ...201122013311
expression and characterization of cryptococcus neoformans recombinant app1.we characterized cryptococcus neoformans recombinant antiphagocytic protein 1 (rapp1) by sds-page, gel filtration chromatography, circular dichroism, and fluorescence spectroscopy. rapp1 produced by c. neoformans var. grubii contains an odd number of cysteines; therefore, it has the ability to form intermolecular disulfide bridges which can lead to the formation of amyloid fibrils in the absence of β-mercaptoethanol or dtt in vitro. alternate approaches to over-expression of rapp1 in the lepidop ...201121971702
identification of novel hybrids between cryptococcus neoformans var. grubii vni and cryptococcus gattii vgii.cryptococcus neoformans and cryptococcus gattii are pathogenic yeasts causing meningoencephalitis in immunocompromised and immunocompetent hosts. the fungus is typically haploid, and sexual reproduction occurs normally between individuals with opposite mating types, α and a. c. neoformans var. grubii (serotype a) is comprised of molecular types vni, vnii, and vnb, and c. neoformans var. neoformans (serotype d) contains the molecular type vniv. additional ...201122081254
contributions of the myd88-dependent receptors il-18r, il-1r, and tlr9 to host defenses following pulmonary challenge with cryptococcus neoformans.signaling via the adapter protein, myd88, is important in the host defense against cryptococcus neoformans infection. while certain toll-like receptors (tlrs) can enhance the clearance of cryptococcus, the contributions of myd88-dependent, tlr-independent pathways have not been fully investigated. we examined the roles of il-1r and il-18r in vivo by challenging c57bl/6 mice with a lethal strain of cryptococcus. we found that the absence of il-18r, but not il-1r, causes a shift in the survival cu ...201122039448
Environmental prevalence of Cryptococcus neoformans and Cryptococcus gattii in India: an update.An overview of work done to-date in India on environmental prevalence, population structure, seasonal variations and antifungal susceptibility of Cryptococcus neoformans and Cryptococcus gattii is presented. The primary ecologic niche of both pathogens is decayed wood in trunk hollows of a wide spectrum of host trees, representing 18 species. Overall, C. neoformans showed a higher environmental prevalence than that of C. gattii which was not found in the avian habitats. Apart from their arboreal ...201122133016
Efficient Regioselective Three-Component Domino Synthesis of 3-(1,2,4-Triazol-5-yl)-1,3-thiazolidin-4-ones as Potent Antifungal and Antituberculosis Agents.In research for promising antibacterial and antifungal compounds, a series of 2-aryl 3-[1,2,4]triazol-5-yl 4-thiazolidinones 1 were synthesized by a domino reaction of 5-amino-1H-[1,2,4]triazoles 3, aromatic aldehydes, and a-mercaptoacids in boiling toluene in the presence of molecular sieves 4 Å. Of the twenty novel 3-[1,2,4]triazol-5-yl 4-thiazolidinone derivatives, four compounds 2-benzo[d][1,3]dioxol-6-yl-3-[(3-morpholin-4-yl)-1H-1,2,4-triazol-5-yl)]-1,3-thiazolidin-4-one (1i), 2-(4-chloroph ...201121932255
Dynamic virulence: real-time assessment of intracellular pathogenesis links Cryptococcus neoformans phenotype with clinical outcome.While a myriad of studies have examined host factors that predispose persons to infection with the opportunistic fungal pathogen Cryptococcus neoformans, comparatively little has been done to examine how virulence factor differences among cryptococcal isolates may impact outcome. In the recent report by Alanio et al. (A. Alanio, M. Desnos-Ollivier, and F. Dromer, mBio 2:e00158-11, 2011), novel flow cytometry-based techniques were employed to demonstrate an association between the phenotype of C. ...201121954307
voriconazole, combined with amphotericin b, in the treatment for pulmonary cryptococcosis caused by c. neoformans (serotype a) in mice with severe combined immunodeficiency (scid).cryptococcosis is a subacute or chronic systemic mycosis with a cosmopolitan nature, caused by yeast of the genus cryptococcus neoformans. the model of systemic cryptococcosis in mice with severe combined immunodeficiency (scid) is useful for immunological and therapeutic study of the disease in immunodeficient hosts. amphotericin b, fluconazole and flucytosine are the drugs most commonly used to treat cryptococcosis. voriconazole is a triazole with high bioavailability, large distribution volum ...201122071662
isolated cryptococcal osteomyelitis in an immunocompetent patient.cryptococcosis is a rare infection in hiv-negative individuals. while the lungs and the central nervous system are most commonly infected, skeletal cryptococcosis is uncommon and isolated osteomyelitis due to cryptococcus neoformans is quite rare. to our knowledge, only 47 cases of isolated cryptococcal osteomyelitis have been reported from 1974 to 2005. we report a case of isolated cryptococcal osteomyelitis in an immunocompetent patient, who received 12 weeks of fluconazole with complete recov ...201121918309
antifungal activity of phenolic-rich lavandula multifida l. essential oil.this study evaluates the antifungal activity and mechanism of action of a new chemotype of lavandula multifida from portugal. the essential oil was analyzed by gas chromatography (gc) and gas chromatography/mass spectrometry (gc/ms), and the minimal inhibitory concentration (mic) and minimal lethal concentration (mlc) of the oil and its major compounds were determined against several pathogenic fungi responsible for candidosis, meningitis, dermatophytosis, and aspergillosis. the influence of the ...201122020493
a β-resorcylic macrolide from the seagrass-derived fungus fusarium sp. psu-es73.a new β-resorcylic macrolide, 5'-hydroxyzearalenone (1), and six known β-resorcylic macrolides were isolated from the seagrass-derived fungus fusarium sp. psu-es73. their structures were established by analysis of spectral data. all of the isolated compounds were evaluated for their antibacterial activity against staphylococcus aureus, both standard and methicillin-resistant strains, as well as their antifungal activity against cryptococcus neoformans. only the known compound zearalenone (2) dis ...201122076763
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