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restricted domain mobility in the candida albicans ess1 prolyl isomerase.ess1 is a peptidyl prolyl cis/trans isomerase that is required for virulence of the pathogenic fungi candida albicans and cryptococcus neoformans. the enzyme isomerizes the phospho-ser-pro linkages in the c-terminal domain of rna polymerase ii. its human homolog, pin1, has been implicated in a wide range of human diseases, including cancer and alzheimer's disease. crystallographic and nmr studies have demonstrated that the sequence linking the catalytic isomerase domain and the substrate binding ...201020304107
cryptococcosis in nonhuman immunodeficiency virus-infected children.between 1991-2006, nine patients below age 18 years, with a microbiologic documentation of cryptococcus neoformans infection and no evidence of human immunodeficiency virus infection, were identified and treated at chang gung children's hospital. all exhibited central nervous system involvement. seven patients were female (age range, 9-16 years; mean age, 13.7 years). five patients (56%) manifested underlying diseases and were receiving either steroid or immunosuppressant treatment at time of di ...201020304330
fungal homoserine kinase (thr1delta) mutants are attenuated in virulence and die rapidly upon threonine starvation and serum incubation.the fungally conserved subset of amino acid biosynthetic enzymes not present in humans offer exciting potential as an unexploited class of antifungal drug targets. since threonine biosynthesis is essential in cryptococcus neoformans, we further explored the potential of threonine biosynthetic enzymes as antifungal drug targets by determining the survival in mice of saccharomyces cerevisiae homoserine kinase (thr1delta) and threonine synthase (thr4delta) mutants. in striking contrast to aspartate ...201020305003
evaluation of the histopathological hepatic lesions and opportunistic agents in brazilian hiv patients.to evaluated the type histopathological hepatic lesions and opportunistic agents in brazilian hiv-infected patients.201020305958
genotypic characterization of environmental isolates of cryptococcus gattii from puerto rico.cryptococcus neoformans and cryptococcus gattii are found in distinct environments with some overlap around different parts of the world. however, no systematic surveys of these two pathogens have been reported from puerto rico, a tropical island uniquely situated between mainland usa and countries in south america. we carried out an exhaustive environmental survey in southwestern puerto rico for pathogenic cryptococcus species. twenty-two presumptive isolates of c. gattii from cacti and tree de ...201020306144
pathogen-specific antibodies: codependent no longer.antibody-mediated defense against pathogens typically requires complex interactions between antibodies and other constituents of the humoral and cellular immune systems. however, recent evidence indicates that some antibodies alone can inhibit pathogen function in the absence of complement, phagocytes, or nk cells. in this issue of the jci, mcclelland et al. have begun to elucidate the molecular bases by which antibodies alone can impact pathogen growth and metabolism. they show that mabs specif ...201020335652
ab binding alters gene expression in cryptococcus neoformans and directly modulates fungal metabolism.abs facilitate humoral immunity via the classical mechanisms of opsonization, complement activation, ab-dependent cellular cytotoxicity, and toxin/viral neutralization. there is also evidence that some abs mediate direct antimicrobial effects. for example, ab binding to the polysaccharide capsule of the human pathogenic fungus cryptococcus neoformans promotes opsonization but also inhibits polysaccharide release and biofilm formation. to investigate whether ab binding affects c. neoformans direc ...201020335660
cerebrospinal fluid hiv-1 viral load during treatment of cryptococcal meningitis. 201020335745
[paraparesis and fever in a tunisian woman: cryptococcal spondylitis with spinal involvement].cryptococcus neoformans is a ubiquitous yeast that causes opportunistic infections mainly involving the central nervous system. cryptococcoma is a rare entity characterized by a solid, tumor-like mass that is usually located in the cerebral hemispheres or cerebellum. spinal involvement is rare with only 6 cases reported in literature. bony involvement is also a rare occurrence that has been observed in only 5 to 10% of reported cases of infection by cryptococcus neofomans. the purpose of this re ...201020337124
immune reconstitution inflammatory syndrome (iris) associated with cryptococcus neoformans infection in aids patients.summary cryptococcosis is frequently associated to the immune reconstitution inflammatory syndrome (iris) in aids patients on highly active antiretroviral therapy (haart). this study aimed to evaluate clinical and evolutive features of iris associated cryptococcosis patients in uberaba, brazil. patients: eighty-one aids individuals admitted at the teaching hospital with cryptococcal meningitis were evaluated and from these, 40 were prospectively followed. of 40 patients with cryptococcosis, nine ...201020337940
could insect phagocytic avoidance by entomogenous fungi have evolved via selection against soil amoeboid predators?the entomopathogenic fungi metarhizium anisopliae and beauveria bassiana are ubiquitously distributed in soils. as insect pathogens they adhere to the insect cuticle and penetrate through to the insect haemocoel using a variety of cuticle-hydrolysing enzymes. once in the insect haemocoel they are able to survive and replicate within, and/or evade, phagocytic haemocyte cells circulating in the haemolymph. the mechanism by which these soil fungi acquire virulence factors for insect infection and i ...201020338910
pleiotropic function of intersectin homologue cin1 in cryptococcus neoformans.the manifestation of virulence traits in cryptococcus neoformans is thought to rely on intracellular transport, a process not fully explored in this pathogenic fungus. through interaction cloning, we identified a multi-modular protein, cin1 (cryptococcal intersectin 1), whose domain structure is similar to that of the human endocytic protein itsn1. cin1 contains an n-terminal eh domain, a central coiled-coil region, a wh2 domain, two sh3 domains and a c-terminal rhogef (dh)-ph domain. interestin ...201020345666
the role of serum cryptococcal antigen screening for the early diagnosis of cryptococcosis in hiv-infected patients with different ranges of cd4 cell counts.to determine the role of serum cryptococcal antigen (sca) for the screening of cryptococcosis in hiv-infected patients with different ranges of cd4 cell counts.201020347868
medically important bacterial-fungal interactions.whether it is in the setting of disease or in a healthy state, the human body contains a diverse range of microorganisms, including bacteria and fungi. the interactions between these taxonomically diverse microorganisms are highly dynamic and dependent on a multitude of microorganism and host factors. human disease can develop from an imbalance between commensal bacteria and fungi or from invasion of particular host niches by opportunistic bacterial and fungal pathogens. this review describes th ...201020348933
fungi and molds following lung transplantation.the landscape of fungal infections in lung transplant recipients has significantly changed over the course of time. the initial predominance of candida species has given way to the prominence of aspergillus species in the current era followed by other mold infections, namely, scedosporium and zygomycetes, which are emerging as newer pathogens. cryptococcus neoformans is another important pathogen responsible for the morbidity in lung transplant recipients. the use of widespread antifungal prophy ...201020354934
[diagnosis of cryptococcal encephalitis in a patient with mature b-cell lymphoblastic leukemia].fungal meningoencephalitides are one of the most menacing infectious complications in hematologic cancer patients in the presence of myelotoxic agranulocytosis. due to diagnostic difficulties, mortality in these cases can be as high as 100%. the causative agent of cryptococcosis is cryptococcus neoformans; damage to the brain arachnoid membranes and substance is diagnosed in 70-90% of cases. unlike bacterial meningitis, the meningeal symptoms typical of cryptococcal meningoencephalitis are not c ...201020364703
disseminated, histologically confirmed cryptococcus spp infection in a domestic ferret.a 4-year-old castrated male domestic ferret from central massachusetts was evaluated for weight loss over a 1.5-month period and for 2 days of retching, diarrhea, and signs of lethargy. it had been housed indoors, with 2 other ferrets, 2 cats, and humans that lacked signs or symptoms of disease.201020367045
cryptococcus neoformans overcomes stress of azole drugs by formation of disomy in specific multiple chromosomes.cryptococcus neoformans is a haploid environmental organism and the major cause of fungal meningoencephalitis in aids patients. fluconazole (flc), a triazole, is widely used for the maintenance therapy of cryptococcosis. heteroresistance to flc, an adaptive mode of azole resistance, was associated with flc therapy failure cases but the mechanism underlying the resistance was unknown. we used comparative genome hybridization and quantitative real-time pcr in order to show that c. neoformans adapt ...201020368972
correlation of etest and neo-sensitabs diffusion assays on mueller-hinton-methylene blue agar with broth microdilution reference method (clsi-m27-a2) for testing susceptibilities of cryptococcus neoformans to amphotericin b and fluconazole.cryptococcus neoformans causes disseminated infection in 7-8% of hiv positive patients admitted to hospital f. j. muñiz in buenos aires. meningoencephalitis is the most frequent clinical manifestation and is one of the main causes of death in those patients with aids. the standard treatment for this mycosis consists of amphotericin b followed by fluconazole until two successive cultures of cfs are negative. although resistance to these drugs is infrequent, minimal inhibitory concentrations (mic) ...201020370370
cryptococcal meningitis after neurosurgery.infection caused by cryptococcus neoformans can affect a variety of patient populations from the immunocompetent host to those who are severely immunocompromised. although the clinical presentation can vary, there is a predilection for invasion of the central nervous system. cryptococcal meningitis is the most common neurologic manifestation. the authors describe a case of an immunocompetent patient who presented with cryptococcal meningitis after a neurosurgical procedure.201020545015
immunomodulatory effects of serotype b glucuronoxylomannan from cryptococcus gattii correlate with polysaccharide diameter.glucuronoxylomannan (gxm), the major capsular component in the cryptococcus complex, interacts with the immune system in multiple ways, which include the activation of toll-like receptors (tlrs) and the modulation of nitric oxide (no) production by phagocytes. in this study, we analyzed several structural parameters of gxm samples from cryptococcus neoformans (serotypes a and d) and cryptococcus gattii (serotypes b and c) and correlated them with the production of no by phagocytes and the activa ...201020547742
effect of cytoskeleton inhibitors on conidiogenesis and capsule in the long neck yeast fellomyces examined by scanning electron microscopy.the aim of this basic study was to investigate by scanning electron microscopy the effects of cytoskeleton inhibitors on conidiogenesis and capsule in the yeast fellomyces fuzhouensis cbs 8243, related to cryptococcus neoformans.201020551635
[cryptococcal meningitis and systemic lupus erythematosus: a case report and review].cryptococcal meningitis is an uncommon but well-known and frequently fatal complication of systemic lupus erythematosus (sle). the clinical manifestations are unspecific and frequently are confused with lupus activity. a patient with cryptococcal meningitis and sle, who responded well to amphotericin deoxycholate therapy, is reported. in a review through medline of the spanish and english literature, 57 cases of sle and cryptococcal meningitis were found. simultaneous presentation of both diseas ...201020556320
the host-infecting fungal transcriptome.the capture of pathogen gene expression signatures directly from the host niche promises to fuel our understanding of the highly complex nature of microbial virulence. however, obtaining and interpreting biological information from infected tissues presents multiple experimental and intellectual challenges, from difficulties in extracting pathogen rna and appropriate choice of experimental design, to interpretation of the resulting infection transcriptome, itself a product of responses to multip ...201020557573
prevalence of the vnic genotype of cryptococcus neoformans in non-hiv-associated cryptococcosis in the republic of korea.pcr fingerprinting and multilocus sequence typing were applied to determine the major molecular types of the cryptococcus neoformans/cryptococcus gattii species complex in the republic of korea. of the 78 strains isolated from patients diagnosed with cryptococcosis between 1990 and 2008, 96% were c. neoformans serotype a, mating type matalpha and molecular type vni. the remaining 4% were c. gattii, serotype b, mating type matalpha and either molecular type vgiib or vgiii. of the 62 strains with ...201020561059
dueling in the lung: how cryptococcus spores race the host for survival.many human fungal pathogens infect people when they are inhaled as spores. despite the serious impact of fungal spores on human health, little is known about their basic properties or how they interact with the host. this is particularly true for cryptococcus neoformans, a human fungal pathogen that causes more than 600,000 deaths annually. spores of c. neoformans have not been well characterized previously because of technical challenges in isolating them; however, recent advances in spore isol ...201020570552
tlr9 signaling is required for generation of the adaptive immune protection in cryptococcus neoformans-infected lungs.to determine whether tlr9 signaling contributes to the development of the adaptive immune response to cryptococcal infection, wild-type (tlr9+/+) and tlr9 knockout (tlr9-/-) balb/c mice were infected intratracheally with 10(4) c. neoformans 52d. we evaluated 1) organ microbial burdens, 2) pulmonary leukocyte recruitment, 3) pulmonary and systemic cytokine induction, and 4) macrophage activation profiles. tlr9 deletion did not affect pulmonary growth during the innate phase, but profoundly impair ...201020581055
cryptococcus neoformans histone acetyltransferase gcn5 regulates fungal adaptation to the host.cryptococcus neoformans is an environmental fungus and an opportunistic human pathogen. previous studies have demonstrated major alterations in its transcriptional profile as this microorganism enters the hostile environment of the human host. to assess the role of chromatin remodeling in host-induced transcriptional responses, we identified the c. neoformans gcn5 histone acetyltransferase and demonstrated its function by complementation studies of saccharomyces cerevisiae. the c. neoformans gcn ...201020581290
life-threatening asymptomatic incidentaloma: a case report of idiopathic cd4 lymphocytopenia and opportunistic infections.incidental lung nodules can be due to a variety of etiologies. management is guided by the most likely or urgent pathology, which is frequently malignancy in an elderly smoker. we present the case of a 62-year-old, long-time smoker, with an incidental lung nodule. pursuit of the underlying etiology revealed disseminated cryptococcal and mycobacterium avium intracellulare infections, which are most often seen in patients with advanced human immunodeficiency virus-acquired immunodeficiency syndrom ...201020581653
fungal cell gigantism during mammalian infection.the interaction between fungal pathogens with the host frequently results in morphological changes, such as hyphae formation. the encapsulated pathogenic fungus cryptococcus neoformans is not considered a dimorphic fungus, and is predominantly found in host tissues as round yeast cells. however, there is a specific morphological change associated with cryptococcal infection that involves an increase in capsule volume. we now report another morphological change whereby gigantic cells are formed i ...201020585557
cryptococcal cell morphology affects host cell interactions and pathogenicity.cryptococcus neoformans is a common life-threatening human fungal pathogen. the size of cryptococcal cells is typically 5 to 10 microm. cell enlargement was observed in vivo, producing cells up to 100 microm. these morphological changes in cell size affected pathogenicity via reducing phagocytosis by host mononuclear cells, increasing resistance to oxidative and nitrosative stress, and correlated with reduced penetration of the central nervous system. cell enlargement was stimulated by coinfecti ...201020585559
a case of pulmonary cryptococcosis caused by capsule-deficient cryptococcus neoformans in an immunocompetent patient. 201020587108
[cap59 gene amplification in cryptococcus neoformans and cryptococcus gattii directly from a yeast suspension].cryptococcus is an encapsulated yeast of class basidiomycetes, etiologic agent of cryptococcosis. cryptococcosis is one of the most common opportunistic infections in immunosuppressed patients, although it can affect immunocompetent individuals. in recent years, the identification of medically important fungal species has been achieved through the amplification of specific regions or genes of fungal dna by polymerase chain reaction (pcr). the cap59 gene is involved in the synthesis of the capsul ...201020589327
radioimmunotherapy is more effective than antifungal treatment in experimental cryptococcal infection.radioimmunotherapy (rit) prolongs the survival of mice infected with cryptococcus neoformans. to compare the efficacy of rit with that of amphotericin b, we infected aj/cr mice intravenously with either nonmelanized or melanized c. neoformans cells. infected mice were either left untreated or treated 24 h after infection with (213)bi-18b7 antibody, amphotericin b, or both. melanization before infection did not increase resistance of c. neoformans to rit in vivo. (213)bi-18b7 treatment almost com ...201020594103
chloride channel-dependent copper acquisition of laccase in the basidiomycetous fungus cryptococcus neoformans.the clc chloride channel gene clc-a of the pathogen yeast cryptococcus neoformans was previously reported to be critical for multicopper laccase activity and growth at an elevated ph. this study reports that copper homeostasis was impaired in the clc-a mutant. this was demonstrated by the substantial decrease of the intracellular quantity of copper under copper-limited growth as determined by flame atomic absorption spectrometry. clc-a is a critical factor in copper homeostasis which is required ...201020596964
melanization of flavonoids by fungal and bacterial laccases.laccase activity in plants results in the formation of a number of brown pigments, often referred to as tannins. laccase-dependent pigment production is also catalogued in numerous fungal and bacterial species. the laccase of the haploid yeast cryptococcus neoformans forms melanin-like pigmentation outside the cell wall in the presence of exogenous substrates. while this process is a contributing factor to its virulence in humans, the evolutionary intent for the laccase function remains a myster ...201021360730
physicochemical properties and antifungal activity of amphotericin b incorporated in cholesteryl carbonate esters.the antifungal activity of amphotericin b (amb) incorporated in three cholesteryl carbonate esters (cces), sodium cholesteryl carbonate, cholesteryl palmityl carbonate, and dicholesteryl carbonate, was examined to assess their potential for use in a dry powder aerosol. formulations containing dissolved amb were stable for 6 months. the particle size varied inversely with liquid crystalline content with observed mass median aerodynamic diameters ranging from 4 to 8 μ m. this was consistent with t ...201021374610
in vitro susceptibility of the yeast pathogen cryptococcus to fluconazole and other azoles varies with molecular genotype.cryptococcosis is primarily caused by cryptococcus neoformans and cryptococcus gattii. these two pathogenic species each divide into four distinct molecular genotypes. in this study, we examined whether genotype influenced susceptibility to antifungal drugs used to treat cryptococcosis using the broth microdilution method described by the clinical and laboratory standards institute. c. gattii isolates belonging to molecular genotype vgii had significantly higher mic values for flucytosine and al ...201020844209
cryptococcal meningoencephalitis with fulminant intracranial hypertension: an unexpected cause of brain death.the diagnosis of brain death requires the presence of unresponsiveness and a lack of receptivity, the absence of movement, breathing and brain stem reflexes, as well as a state of coma in which the cause has been identified. we report a case of brain death that was diagnosed based on clinical neurological examinations, and supported by the absence of cerebral blood flow on magnetic resonance angiography and electroencephalography demonstrating the characteristic absence of electrical activity. t ...201020848052
synthesis and antifungal activity of benzofuran-5-ols.benzofuran-5-ol derivatives were synthesized and tested for in vitro antifungal activity against candida, aspergillus species, and cryptococcus neoformans. among them tested, many benzofuran-5-ols showed good antifungal activity. the results suggest that benzofuran-5-ols would be promising antifungal agents.201020851600
regulation of virulence factors, carbon utilization and virulence by snf1 in cryptococcus neoformans jec21 and divergent actions of snf1 between cryptococcal strains.we describe here the functions of a snf1/ampk homolog in the human pathogenic yeast cryptococcus neoformans, strain jec21. we found that jec21 snf1 is a key regulator for the biosynthesis of the major virulence factors, stress resistance and alternative carbon source utilization. disruption of jec21 snf1 results in defects of laccase activity and capsule production, sensitivity to cation stress. especially, we found that jec21 snf1 is essential for growth at elevated temperature and for thermoto ...201020719250
mechanisms of cryptococcal virulence and persistence.cryptococcus neoformans is an environmental yeast that is a leading cause of fatal mycosis in aids patients and a major cause of meningoencephalitis and cns-related mortality around the globe. although c. neoformans infection is mostly a manifestation of immune deficiency, up to 25% of cases reported in the usa occur in patients without recognizable immune defects, indicating that c. neoformans can develop mechanisms that allow it to evade immune defenses and persist in noncompromised hosts. thi ...201020722603
role of sphingomyelin synthase in controlling the antimicrobial activity of neutrophils against cryptococcus neoformans.the key host cellular pathway(s) necessary to control the infection caused by inhalation of the environmental fungal pathogen cryptococcus neoformans are still largely unknown. here we have identified that the sphingolipid pathway in neutrophils is required for them to exert their killing activity on the fungus. in particular, using both pharmacological and genetic approaches, we show that inhibition of sphingomyelin synthase (sms) activity profoundly impairs the killing ability of neutrophils b ...201021203393
automated analysis of cryptococcal macrophage parasitism using gfp-tagged cryptococci.the human fungal pathogens cryptococcus neoformans and c. gattii cause life-threatening infections of the central nervous system. one of the major characteristics of cryptococcal disease is the ability of the pathogen to parasitise upon phagocytic immune effector cells, a phenomenon that correlates strongly with virulence in rodent models of infection. despite the importance of phagocyte/cryptococcus interactions to disease progression, current methods for assaying virulence in the macrophage sy ...201021209844
the role of exon shuffling in shaping protein-protein interaction networks.physical protein-protein interaction (ppi) is a critical phenomenon for the function of most proteins in living organisms and a significant fraction of ppis are the result of domain-domain interactions. exon shuffling, intron-mediated recombination of exons from existing genes, is known to have been a major mechanism of domain shuffling in metazoans. thus, we hypothesized that exon shuffling could have a significant influence in shaping the topology of ppi networks.201021210967
synthesis and antifungal activity of furo[2,3-f]quinolin-5-ols.furo[2,3-f]quinolin-5-ol derivatives were synthesized and tested for in vitro antifungal activity against candida,aspergillus species, and cryptococcus neoformans. among them tested, many furo[2,3-f]quinolin-5-ols showed good antifungal activity. the results suggest that furo[2,3-f]quinolin-5-ols would be promising antifungal agents.201021215618
chemokine receptor 2-mediated accumulation of fungicidal exudate macrophages in mice that clear cryptococcal lung infection.clearance of pulmonary infection with the fungal pathogen cryptococcus neoformans is associated with the accumulation and activation of lung macrophages. however, the phenotype of these macrophages and the mechanisms contributing to their accumulation are not well-defined. in this study, we used an established murine model of cryptococcal lung infection and flow cytometric analysis to identify alveolar macrophages (ams) and the recently described exudate macrophages (exms). exudate macrophages a ...201021224057
cryptococcus neoformans var. grubii - pathogenicity of environmental isolates correlated to virulence factors, susceptibility to fluconazole and molecular profile.the pathogenicity of cryptococcus neoformans is heterogeneous and is associated with the expression of virulence factors. this study aimed to correlate the pathogenicity of c. neoformans var. grubii in balb/c mice with in vitro virulence factors, fluconazole minimal inhibitory concentrations (mics) and molecular profiles, before and after animal passage. ten environmental isolates and one atcc strain of c. neoformans var. grubii mating type α were evaluated. most isolates (91%) killed 50% or mor ...201021225196
[case of pulmonary cryptococcosis which developed in a patient receiving abatacept therapy for rheumatoid arthritis].a 59-year-old woman who had been receiving abatacept therapy for rheumatoid arthritis was noted to have multiple nodules in both lungs on routine chest x-ray films. chest computed tomography (ct) revealed multiple nodules with small cavities in both lung fields. the cryptococcus neoformans antigen was detected from her serum and bronchial lavage fluids, indicating a diagnosis of pulmonary cryptococcosis. abatacept was discontinued, and antifungal treatment with fluconazole was started. the lung ...201021226309
case report-right iliac fossa mass in an hiv-positive woman. cryptococcal meningitis. 201021614883
cryptococcosis presenting as anterior neck swelling in an immunocompetent man: a case report.cryptococcosis is caused by the encapsulated opportunistic yeast cryptococcus neoformans. an immunocompromised host is more susceptible to the survival and dissemination of this yeast, which can occur to almost all organs of the body, especially the central nervous system, lungs, bone marrow, gastrointestinal tract, retina, and reticuloendothelial system. however, there are few reports of cryptococcus causing infections ir immunocompetent hosts.201021428161
identification and functional characterization of a cryptococcus neoformans upc2 homolog.azoles are currently the most widely used class of antifungal drugs clinically, and are effective for treating fungal infections. target site of azoles is ergosterol biosynthesis in fungal cell membrane, which is absent in the mammalian host. however, the development of resistance to azole treatments in the fungal pathogen has become a significant challenge. here, we report the identification and functional characterization of a upc2 homolog in the human pathogen cryptococcus neoformans. upc2 pl ...201023956658
disseminated cryptococcus neoformans infection and crohn's disease in an immunocompetent patient.cryptococcus neoformans is a human pathogen ubiquitously present in the environment. it primarily affects immunocompromised patients, but individuals with no underlying disease or immunodeficiency can also be affected. we herein describe the case of a patient found to have crohn's disease and disseminated cryptococcosis simultaneously. she had no predisposing underlying cause for impaired immunity. our patient showed signs that would have make it hard to discriminate between an inflammatory bowe ...201021272807
antibacterial and antifungal activities from siamese crocodile blood.to evaluate the in vitro antimicrobial activity of the siamese crocodile blood against bacteria and fungi.201021294399
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
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
susceptibility profile of clinical isolates of non-cryptococcus neoformans/non-cryptococcus gattii cryptococcus species and literature review.the in vitro susceptibility profile of 24 clinical isolates of non-cryptococcus neoformans/non-cryptococcus gattii cryptococcus species was analysed. in addition, the susceptibility results of 98 other strains from seven different reports were reviewed. the latter included studies which used antifungal susceptibility testing reference procedures or commercial methods which exhibited high correlation rates with the reference procedures. a total of 122 isolates were analysed (57 cryptococcus albid ...201019235546
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
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
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
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
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
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
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
plant production of anti-ß-glucan antibodies for immunotherapy of fungal infections in humans.there is an increasing interest in the development of therapeutic antibodies (ab) to improve the control of fungal pathogens, but none of these reagents is available for clinical use. we previously described a murine monoclonal antibody (mab 2g8) targeting ß-glucan, a cell wall polysaccharide common to most pathogenic fungi, which conferred significant protection against candida albicans, aspergillus fumigatus and cryptococcus neoformans in animal models. transfer of this wide-spectrum, antifung ...201121265996
comparative genomics allowed the identification of drug targets against human fungal pathogens.the prevalence of invasive fungal infections (ifis) has increased steadily worldwide in the last few decades. particularly, there has been a global rise in the number of infections among immunosuppressed people. these patients present severe clinical forms of the infections, which are commonly fatal, and they are more susceptible to opportunistic fungal infections than non-immunocompromised people. ifis have historically been associated with high morbidity and mortality, partly because of the li ...201121272313
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
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
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