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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
concurrent infection with cryptococcus neoformans/gattii species complex and mycobacterium avium affecting the subcutis and bone of a pelvic limb in a cat.this paper describes a cat with severe localised infections with cryptococcus neoformans/gattii species complex and mycobacterium avium affecting the subcutis and underlying fascia and bone of the right pelvic limb. the simultaneous isolation of both pathogens in this patient was unexpected and posed unique issues concerning both diagnosis and clinical management. the aetiopathogenesis of this infection is discussed in relation to aspects of diagnosis and therapy.201121820926
high resolution melting (hrm) analysis for the identification of cryptococcus neoformans-cryptococcus gattii complex.we have developed a two-step method based on high resolution melting (hrm) that reliably identifies species from the cryptococcus species complex (c.neoformans var. grubii, c. neoformans var. neoformans and c. gattii). our results indicate that hrm can provide a fast protocol to identify and distinguish among the main cryptococcus spp.201121832024
posaconazole: a new antifungal weapon.the last twenty years, the incidence of invasive fungal infections (ifi) has risen dramatically due to the prolongation of survival of patients with multiple risk factors for fungal infections. amphotericin b was for more than 40 years the gold standard for almost all ifi, but toxicity and resistance, especially of new and emerging pathogens remained important issues. fluconazole and itraconazole have also the same disadvantage of resistance. voriconazole, a new triazole antifungal has offered a ...201121682687
calcineurin co-localizes with p-bodies and stress granules during thermal stress in cryptococcus neoformans.calcineurin is a calcium-calmodulin-activated serine-threonine specific phosphatase that operates during cellular responses to stress and plays a prominent role in transcriptional control whereas regulatory events beyond transcription are less well characterized. this study reveals a novel transcription-independent role of calcineurin during temperature-stress response in the human fungal pathogen cryptococcus neoformans. the diffusely cytoplasmic calcineurin catalytic subunit cna1 relocates to ...201121724937
evaluation of cryptococcus neoformans galactoxylomannan-protein conjugate as vaccine candidate against murine cryptococcosis.galactoxylomannan (galxm) is a complex polysaccharide produced by the human pathogenic fungus cryptococcus neoformans that mediates profound immunological derangements in murine models. galxm is essentially non-immunogenic and produces immune paralysis in mice. previous studies have attempted to enhance immunogenicity by conjugating galxm to a protein carrier, but only transient antibody responses were elicited. here we report the generation of two galxm conjugates with bovine serum albumin (bsa ...201121238568
role of glucose in the expression of cryptococcus neoformans antiphagocytic protein 1, app1.the cryptococcus-specific protein antiphagocytic protein 1 (app1) regulates cryptococcus neoformans virulence by controlling macrophage-driven fungal phagocytosis. this is accomplished through complement receptors (cr), specifically cr3. when inhaled, c. neoformans can cause a life-threatening meningoencephalitis in immunocompromised patients. because glucose starvation can significantly change the gene expression and virulence of c. neoformans and because app1 is critical for phagocytosis in th ...201121239626
fungal bloodstream infections in tertiary care hospitals in colombia.fungal infections have increased in critical care patients, causing high morbidity and mortality.201121241818
antifungal activity of xanthones: evaluation of their effect on ergosterol biosynthesis by high-performance liquid chromatography.the increasing resistance of pathogenic fungi to antifungal compounds and the reduced number of available drugs led to the search for therapeutic alternatives among natural products, including xanthones. the antifungal activity of 27 simple oxygenated xanthones was evaluated by determination of their minimal inhibitory concentration on clinical and type strains of candida, cryptococcus, aspergillus and dermatophytes, and their preponderance on the dermatophytic filamentous fungi was observed. fu ...201121244637
process analysis of variables for standardization of antifungal susceptibility testing of nonfermentative yeasts.nonfermentative yeasts, such as cryptococcus spp., have emerged as fungal pathogens during the last few years. however, standard methods to measure their antifungal susceptibility (antifungal susceptibility testing [ast]) are not completely reliable due to the impaired growth of these yeasts in standard media. in this work, we have compared the growth kinetics and the antifungal susceptibilities of representative species of nonfermentative yeasts such as cryptococcus neoformans, cryptococcus gat ...201121245438
hyrtioseragamines a and b, new alkaloids from the sponge hyrtios species.two novel alkaloids with a furo[2,3-b]pyrazin-2(1h)-one moiety and a guanidino group, hyrtioseragamines a (1) and b (2), have been isolated from an okinawan marine sponge hyrtios species. the structures of 1 and 2 were elucidated on the basis of spectroscopic data and chemical conversions. compounds 1 and 2 are the first natural products possessing a furo[2,3-b]pyrazine-related moiety.201121247076
prevalence of yeast-like fungi and evaluation of several virulence factors from feral pigeons in seoul, korea.studies of pigeon-borne yeasts have tended to focus on species, such as cryptococcus neoformans and candida albicans, with scant attention to feral pigeons in korea. we studied the prevalence of yeasts from faecal samples of feral pigeons obtained in various public places in seoul, korea, and assessed their potential capacity as human pathogens.201121251028
cutaneous cryptococcal infection as a manifestation of disseminated disease. cryptococcus neoformans. 201121251522
in vitro antifungal susceptibility pattern and ergosterol content in clinical yeast strains.absence or severe reduction in the amount of ergosterol in the fungal membrane and its replacement with other sterols have been described as potential antifungal resistance mechanisms in fungi.201121251996
environmental isolation of cryptococcus gattii serotype b, vgi/matα strains in southern italy.until recently, cryptococcus gattii was believed to be endemic in tropical and subtropical regions. to date, it has unexpectedly emerged as primary pathogen in temperate climate indicating that it has evolved and adapted to new environmental conditions including those existing in the mediterranean area. earlier attempts to isolate c. gattii from our environment were unsuccessful but this time, 18 years after the last environmental screening for c. neoformans, we isolated c. gattii from eucalyptu ...201121253853
the endocytic adaptor proteins of pathogenic fungi: charting new and familiar pathways.intracellular transport is an essential biological process that is highly conserved throughout the eukaryotic organisms. in fungi, adaptor proteins implicated in the endocytic cycle of endocytosis and exocytosis were found to be important for growth, differentiation, and/or virulence. for example, saccharomyces cerevisiae pan1 is an endocytic protein that regulates membrane trafficking, the actin cytoskeleton, and signaling. in cryptococcus neoformans, a multi-modular endocytic protein, cin1, wa ...201121254965
pulmonary cryptococcus infection after mono-chemotherapy with gemcitabine.mono-chemotherapy with gemcitabine (difluorodeoxycytidine) is an effective cancer chemotherapy, and is often used instead of a more effective but more toxic combination chemotherapy regimen. infection associated with gemcitabine is very rare. we present a case of cryptococcus neoformans pneumonia that developed after 5 courses of gemcitabine for advanced bladder carcinoma. lung biopsy and antigens demonstrated c. neoformans. the pneumonia resolved after antifungal therapy.201121255489
characterization of inositol phospho-sphingolipid-phospholipase c 1 (isc1) in cryptococcus neoformans reveals unique biochemical features.in this work, we biochemically characterized inositol phosphosphingolipid-phospholipase c (isc1) from the pathogenic fungus cryptococcus neoformans. unlike isc1 from other fungi and parasites which hydrolyze both fungal complex sphingolipids (ipc-plc) and mammalian sphingomyelin (sm-plc), c. neoformans isc1 only exerts ipc-plc activity. genetic mutations thought to regulate substrate recognition in other isc1 proteins do not restore sm-plc activity of the cryptococcal enzyme. c. neoformans isc1 ...201121256847
the pathogenic fungus paracoccidioides brasiliensis exports extracellular vesicles containing highly immunogenic α-galactosyl epitopes.exosome-like vesicles containing virulence factors, enzymes, and antigens have recently been characterized in fungal pathogens, such as cryptococcus neoformans and histoplasma capsulatum. here, we describe extracellular vesicles carrying highly immunogenic α-linked galactopyranosyl (α-gal) epitopes in paracoccidioides brasiliensis. p. brasiliensis is a dimorphic fungus that causes human paracoccidioidomycosis (pcm). for vesicle preparations, cell-free supernatant fluids from yeast cells cultivat ...201121216942
invasive bacterial and fungal infections among hospitalized hiv-infected and hiv-uninfected adults and adolescents in northern tanzania.few studies describe patterns of human immunodeficiency virus (hiv) co-infections in african hospitals in the antiretroviral therapy (art) era.201121217181
transmission of cryptococcus neoformans by organ transplantation.this article describes transmission of cryptococcus neoformans by solid organ transplantation.201121220771
loss-of-function mutation of reduced wall acetylation2 in arabidopsis leads to reduced cell wall acetylation and increased resistance to botrytis cinerea.nearly all polysaccharides in plant cell walls are o-acetylated, including the various pectic polysaccharides and the hemicelluloses xylan, mannan, and xyloglucan. however, the enzymes involved in the polysaccharide acetylation have not been identified. while the role of polysaccharide acetylation in vivo is unclear, it is known to reduce biofuel yield from lignocellulosic biomass by the inhibition of microorganisms used for fermentation. we have analyzed four arabidopsis (arabidopsis thaliana) ...201121212300
clinicopathologic and ultrastructural study of non-hiv-related primary pulmonary cryptococcosis in china: report of 43 cases.to clarify the clinicopathologic and ultrastructural features of primary pulmonary cryptococcosis (pc).201121214404
evidence for branching in cryptococcal capsular polysaccharides and consequences on its biological activity.the encapsulated fungus cryptococcus neoformans is a common cause of life-threatening disease in immunocompromised individuals. its major virulence determinant is the polysaccharide (ps) capsule. an unsolved problem in cryptococcal biology is whether the pss composing the capsule are linear or complex branched polymers, as well as the implications of this structural composition in pathogenesis. in this study we approached the problem by combining static and dynamic light scattering, viscosity an ...201121208301
mediastinal cryptococcosis masquerading as therapy-refractory lymphoma. 201120730538
seasonal variations in the prevalence of cryptococcus neoformans var. grubii and cryptococcus gattii in decayed wood inside trunk hollows of diverse tree species in north-western india: a retrospective study.this study presents a 7-year retrospective analysis of seasonal variations in the prevalence of cryptococcus neoformans var. grubii and cryptococcus gattii in decayed wood inside trunk hollows of 518 trees belonging to 20 species in north-western india during 2000-2007. of the 1,439 wood samples investigated, 406 (28.2%) were found to be positive for the cryptococcus neoformans species complex which included 247 samples from which c. neoformans var. grubii was recovered and 171 which yielded c. ...201120854229
mri findings of cerebral cryptococcosis in immunocompetent patients.worldwide, cerebral cryptococcal infections caused by cryptococcus neoformans are mostly found in immunocompromised patients, but less found in immunocompetent patients with fewer related imaging reports in literatures. this pictorial essay describes some important mr imaging features in arriving at diagnosis for cerebral cryptococcosis in immunocompetent patients by way of five illustrative cases with intact mri data.201121382189
effect of cytokine interplay on macrophage polarization during chronic pulmonary infection with cryptococcus neoformans.the immune response to cryptococcus neoformans following pulmonary infection of c57bl/6 wild-type (wt) mice results in the development of persistent infection with characteristics of allergic bronchopulmonary mycosis (abpm). to further clarify the role of th1/th2 polarizing cytokines in this model, we performed kinetic analysis of cytokine responses and compared cytokine profiles, pathologies, and macrophage (mac) polarization status in c. neoformans-infected wt, interleukin-4-deficient (il-4(-/ ...201121383052
difficulty diagnosing chronic cryptococcal meningitis in idiopathic cd4+ lymphocytopenia.a 64-year-old man with idiopathic cd4(+) lymphocytopenia developed cognitive impairment and gait ataxia with isolated obstructive hydrocephalus, which was fatal. cerebrospinal fluid showed mild pleocytosis, but the etiology was not revealed by extensive analysis. at autopsy, inflammatory cells, cd8(+) lymphocytes and abundant macrophages but not cd4(+) lymphocytes were infiltrating the meninges at the base of the brain. electron microscopy demonstrated that inflammation was caused by cryptococcu ...201121384279
antiparasitic and antimicrobial indolizidines from the leaves of prosopis glandulosa var. glandulosa*a new indolizidine alkaloid, named +ö(1,6)-juliprosopine ( 1), together with previously known indolizidine analogs ( 2- 6), was isolated from the leaves of prosopis glandulosa var. glandulosa, collected from nevada, usa; while two other known indolizidines, juliprosopine ( 6) and juliprosine ( 7), were isolated from p. glandulosa leaves collected in texas, usa. the structures of compound 1 and 7 were determined using a combination of nmr and ms techniques. compound 7 exhibited potent antiplasmod ...201121384317
successful liver transplantation from a living donor with asymptomatic pulmonary cryptococcosis. 201121384521
asymmetric chemoenzymatic synthesis of miconazole and econazole enantiomers. the importance of chirality in their biological evaluation.a simple and novel chemoenzymatic route has been applied for the first time in the synthesis of miconazole and econazole single enantiomers. lipases and oxidoreductases have been tested in stereoselective processes; the best results were attained with oxidoreductases for the introduction of chirality in an adequate intermediate. the behaviors of a series of ketones and racemic alcohols in bioreductions and acetylation procedures, respectively, have been investigated; the best results were found ...201121384803
glucuronoxylomannan from cryptococcus neoformans down-regulates the enzyme 6-phosphofructo-1-kinase of macrophages.the encapsulated yeast cryptococcus neoformans is the causative agent of cryptococosis, an opportunistic life-threatening infection. c. neoformans is coated by a polysaccharide capsule mainly composed of glucuronoxylomannan (gxm). gxm is considered a key virulence factor of this pathogen. the present work aimed at evaluating the effects of gxm on the key glycolytic enzyme, 6-phosphofructo-1-kinase (pfk). gxm inhibited pfk activity in cultured murine macrophages in both dose- and time-dependent m ...201121388964
in vitro antifungal susceptibility profiles and genotypes of 308 clinical and environmental isolates of cryptococcus neoformans var. grubii and cryptococcus gattii serotype b from north-western india.cryptococcus neoformans and cryptococcus gattii are aetiological agents of cryptococcosis, a major opportunistic systemic mycosis of increasing global importance. this study reports the antifungal susceptibility profiles of clinical and environmental isolates of c. neoformans var. grubii, genotype vni/aflp1 (nôçè=ôçè246), and c. gattii serotype b, genotype vgi/aflp4 (nôçè=ôçè62), originating from patients and environmental sources in north-western india. all of the c. neoformans var. grubii and ...201121393452
cryptococcal abscess and osteomyelitis of the proximal phalanx of the hand. 201121393928
two major inositol transporters and their role in cryptococcal virulence.cryptococcus neoformans is an aids-associated human fungal pathogen and the most common cause of fungal meningitis, with a mortality rate over 40% in aids patients. significant advances have been achieved in understanding its disease mechanisms. yet the underlying mechanism of a high frequency of cryptococcal meningitis remains unclear. the existence of high inositol concentrations in brain and our earlier discovery of a large inositol transporter (itr) gene family in c. neoformans led us to inv ...201121398509
a two-gene balance regulates salmonella typhimurium tolerance in the nematode caenorhabditis elegans.lysozymes are antimicrobial enzymes that perform a critical role in resisting infection in a wide-range of eukaryotes. however, using the nematode caenorhabditis elegans as a model host we now demonstrate that deletion of the protist type lysozyme lys-7 renders animals susceptible to killing by the fatal fungal human pathogen cryptococcus neoformans, but, remarkably, enhances tolerance to the enteric bacteria salmonella typhimurium. this trade-off in immunological susceptibility in c. elegans is ...201121399680
preventing phagocytosis takes more than a sweet disposition.while a polysaccharide capsule is known to be important for preventing phagocytosis of the human pathogen cryptococcus neoformans, other antiphagocytic pathways have been generally elusive. now, a capsule-independent pathway has been identified that prevents macrophages from ingesting the fungus, contributing to evasion of the host immune response.201121402356
a major role for capsule-independent phagocytosis-inhibitory mechanisms in mammalian infection by cryptococcus neoformans.the antiphagocytic polysaccharide capsule of the human fungal pathogen cryptococcus neoformans is a major virulence attribute. however, previous studies of the pleiotropic virulence determinant gat201, a gata family transcription factor, suggested that capsule-independent antiphagocytic mechanisms exist. we have determined that gat201 controls the mrna levels of ~1100 genes (16% of the genome) and binds the upstream regions of ~130 genes. seven gat201-bound genes encode for putative and known tr ...201121402362
optimization of 3-(phenylthio)quinolinium compounds against opportunistic fungal pathogens.ring-opened benzothieno[3,2-b]quinolinium salts (3) were designed and synthesized with substitution on the thiophene moiety. in vitro screenings were carried out against fungal pathogens including cryptococcus neoformans, candida albicans, candida glabrata, candida krusei and aspergillus fumigatus. in all, by replacing the n-methyl group (2) with n-?-phenylpentyl or ?-cyclohexylpentyl group to form substituted 3-(phenylthio)quinolinium compounds produced remarkable potencies, as high as 300-fold ...201121402432
carbonic anhydrase inhibitors. inhibition of the ß-class enzymes from the fungal pathogens candida albicans and cryptococcus neoformans with branched aliphatic/aromatic carboxylates and their derivatives.the inhibition of the ß-carbonic anhydrases (cas, ec 4.2.1.1) from the pathogenic fungi cryptococcus neoformans (can2) and candida albicans (nce103) with a series of 25 branched aliphatic and aromatic carboxylates has been investigated. human isoforms hca i and ii were also included in the study for comparison. aliphatic carboxylates were generally millimolar hca i and ii inhibitors and low micromolar/submicromolar ß-ca inhibitors. aromatic carboxylates were micromolar inhibitors of the four enz ...201121402476
design, synthesis and antifungal activities of novel 1,2,4-triazole derivatives.a series of novel 1,2,4-triazole derivatives with a 4-(4-substitutedphenyl) piperazine side chain were designed and synthesized based on the structure of lanosterol 14a-demethylase (cyp51). their antifungal activities against eight human pathogenic fungi were evaluated in vitro by measuring the minimal inhibitory concentrations. nearly all tested compounds were found to be more potent against candida albicans than control drug fluconazole. noticeably, the mic(80) value of compounds 6,7,9,14 and ...201121420761
[effect of hiv-1gp41 ectodomain on cryptococcus neoformans-induced cytoskeletal changes in human brain microvascular endothelial cells].to study the effect of hiv-1 gp41 ectodomain (gp41-i90) on the cytoskeletal changes in human brain microvascular endothelial cells (hbmecs) induced by cryptococcus neoformans.201121421487
an altered camelid-like single domain anti-idiotypic antibody fragment of hm-1 killer toxin: acts as an effective antifungal agent.phage-display and competitive panning elution leads to the identification of minimum-sized antigen binders together with conventional antibodies from a mouse cdna library constructed from hm-1 killer toxin neutralizing monoclonal antibody (nmab-kt). antigen-specific altered camelid-like single-domain heavy chain antibody (scfv k2) and a conventional antibody (scfv k1) have been isolated against the idiotypic antigen nmab-kt. the objectives of the study were to examine (1) their properties as com ...201121305279
endophytic fungi from dragon's blood specimens: isolation, identification, phylogenetic diversity and bioactivity.endophytic fungi from dragon's blood specimens of different locations of china were characterized taxonomically and investigated concerning their antimicrobial and antitumor activity against six pathogenic microbes and five tumor cells. a total of 49 endophytic fungi were obtained from dragon's blood materials of dracaena spp., 18 taxa were represented by 43 (87.8%) isolates and only six (12.2%) isolates were unknown. twenty (40.8%) of the isolates displayed antimicrobial activity against at lea ...201121305629
the ime2 protein kinase family in fungi: more duties than just meiosis.ime2 of the budding yeast saccharomyces cerevisiae belongs to a family of conserved protein kinases displaying sequence similarities to both cyclin-dependent kinases and mitogen-activated protein kinases. ime2 has a pivotal role for meiosis and sporulation. the involvement of this protein kinase in the regulation of various key events in meiosis, such as the initiation of dna replication, the expression of meiosis-specific genes and the passage through the two consecutive rounds of nuclear divis ...201121306447
amphotericin b mediates killing in cryptococcus neoformans through the induction of a strong oxidative burst.we studied the effects of amphotericin b (amb) on cryptococcus neoformans using different viability methods (cfus enumeration, xtt assay and propidium iodide permeability). after 1h of incubation, there were no viable colonies when the cells were exposed to amb concentrations = 1 mg/l. in the same conditions, the cells did not become permeable to propidium iodide, a phenomenon that was not observed until 3h of incubation. when viability was measured in parallel using xtt assay, a result consiste ...201121310262
synthesis, stereochemistry, antimicrobial evaluation and qsar studies of 2,6-diaryltetrahydropyran-4-one thiosemicarbazones.a series of 2,6-diaryltetrahydropyran-4-one thiosemicarbazones (11-27) were synthesized and characterized for evaluation of potential antibacterial activity against staphylococcus aureus, escherichia coli, pseudomonas aeruginosa, salmonella typhi, bacillus subtilis and klebsiella pneumonia and antifungal activity against cryptococcus neoformans, candida albicans, rhizopus sp., aspergillus niger and aspergillus flavus were evaluated. compounds 21 and 22 showed maximum inhibition potency at low co ...201121316819
mechanisms of unisexual mating in cryptococcus neoformans.sex serves a pivotal role in genetic exchange and it contributes to the fitness and genetic diversity for eukaryotic populations. although the importance of the canonical bisexual mating has been widely accepted, the significance of the evolution and maintenance of unisexual mating observed in some eukaryotes is unclear. the recent discovery of same-sex mating in the human fungal pathogen cryptococcus neoformans and the revelation of its impact on the cryptococcus global population structure pro ...201121320625
chemical composition and antifungal activity of the essential oils of lavandula viridis l'her.in the present work we report for what we believe to be the first time the antifungal activity and mechanism of action of the essential oils of lavandula viridis from portugal. the essential oils were isolated by hydrodistillation and analysed by gc and gc/ms. the mic and the minimal lethal concentration (mlc) of the essential oil and its major compounds were determined against several pathogenic fungi. the influence of subinhibitory concentrations of the essential oil on the dimorphic transitio ...201121321363
synthesis of some novel 3-(1-(1-substitutedpiperidin-4-yl)-1h-1,2,3-triazol-4-yl)-5-substituted phenyl-1,2,4-oxadiazoles as antifungal agents.a novel series of 3-(1-(1-substituted piperidin-4-yl)-1h-1,2,3-triazol-4-yl)-5-substituted phenyl-1,2,4-oxadiazoles bearing 1,2,3-triazole and piperidine ring has been synthesized in one step from amidoxime using carbonyl diimidazole (cdi) and k(2)co(3). all the synthesized compounds (4a-4r) are novel and evaluated for their in vitro antifungal activities. sar for the series has been developed by comparing their mic values with miconazole and fluconazole. some of the compounds from the series li ...201121324567
expanding fungal pathogenesis: cryptococcus breaks out of the opportunistic box.cryptococcus neoformans is generally considered to be an opportunistic fungal pathogen because of its tendency to infect immunocompromised individuals, particularly those infected with hiv. however, this view has been challenged by the recent discovery of specialized interactions between the fungus and its mammalian hosts, and by the emergence of the related species cryptococcus gattii as a primary pathogen of immunocompetent populations. in this review, we highlight features of cryptococcal pat ...201121326274
a fatal case of meningitis caused by cryptococcus neoformans var. grubii in an immunocompetent male.the incidence of cryptococcal infection is high in developing countries such as india. cryptococcal meningitis is considered rare in immunocompetent patients and is mainly a disease of immunocompromised patients. prognosis in immunocompetent patients is generally considered good. we report a fatal case of cryptococcal meningitis in an immunocompetent male caused by cryptococcus neoformans var. grubii. whether the patient is immunocompromised or immunocompetent, the outcome of the disease can be ...201121330745
natural product-based phenols as novel probes for mycobacterial and fungal carbonic anhydrases.in order to discover novel probes that may help in the investigation and control of infectious diseases through a new mechanism of action, we have evaluated a library of phenol-based natural products (nps) for enzyme inhibition against four recently characterized pathogen ß-family carbonic anhydrases (cas). these include cas from mycobacterium tuberculosis, candida albicans, and cryptococcus neoformans as well as a-family human ca i and ca ii for comparison. many of the nps selectively inhibited ...201121332115
enhanced activity of antifungal drugs using natural phenolics against yeast strains of candida and cryptococcus.determine whether certain, natural phenolic compounds enhance activity of commercial antifungal drugs against yeast strains of candida and cryptococcus neoformans.201121332761
feline cryptococcosis: impact of current research on clinical management.disease summary: cryptococcosis, principally caused by cryptococcus neoformans and cryptococcus gattii, is the most common systemic mycosis of cats worldwide. cats may be infected following inhalation of spores from the environment, with the nasal cavity suspected as being the initial site of colonization and subsequent infection. other sites of infection in cats are the skin, lungs, lymph nodes, central nervous system (cns), eyes and, occasionally, periarticular connective tissue. cryptococcosi ...201121338941
quantification of cerebrospinal fluid lactic acid in the differential diagnosis between hiv chronic meningitis and opportunistic meningitis.approximately 40% of hiv infected patients have chronic meningitis at various stages during the infection, 59% are asymptomatic. this is a diagnosis of exclusion and a confounding factor in cerebrospinal fluid (csf) analysis, any other causes of chronic meningitis by opportunistic or co-infection must be ruled out. the aim of this study was to analyze csf lactic acid (la) as an adjuvant biomarker in chronic meningitis due to hiv.201121345043
wsp1, a gbd/crib domain-containing wasp homolog, is required for growth, morphogenesis, and virulence of cryptococcus neoformans.human endocytic protein itsn1 regulates actin reorganization by activating rho family gtpases, such as cdc42. the process is enhanced by itsn binding of wasp, an effector of cdc42 and a potent activator of actin polymerization. in the human pathogen cryptococcus neoformans, endocytic protein cin1 also interacts with cdc42 and wsp1, an uncharacterized wasp homolog, but the significance of these interactions remains unknown. wsp1 contains several conserved domains, including a wasp homology 1 doma ...201121357479
role of il-17a on resolution of pulmonary c. neoformans infection.the current studies evaluated the role of interleukin (il)-17a in the induction of protective immunity against pulmonary cryptococcosis in mice. protection against pulmonary infection with c. neoformans strain h99? was associated with increased il-17a production. signaling through the ifn-? receptor (r) was required for increased il-17a production, however, a th17-type cytokine profile was not observed. neutrophils were found to be the predominant leukocytic source of il-17a, rather than t cells ...201121359196
the human ku autoantigen shares amino acid sequence homology with fungal, but not bacterial and viral, proteins.context: molecular mimicry between autoantigens and microbial antigens is a possible triggering mechanism of autoimmunity. human ku is a dna-associated autoantigen targeted by autoantibodies in patients with systemic lupus erythematosus and related disorders; available data are consistent with a role of molecular mimicry in the pathogenesis of anti-ku autoimmunity, but no research exist on this topic. objective: we aimed to define the most probable microbial triggers of anti-ku autoimmunity via ...201120718578
the gata-type transcriptional activator gat1 regulates nitrogen uptake and metabolism in the human pathogen cryptococcus neoformans.nitrogen uptake and metabolism are essential to microbial growth. gat1 belongs to a conserved family of zinc finger containing transcriptional regulators known as gata-factors. these factors activate the transcription of nitrogen catabolite repression (ncr) sensitive genes when preferred nitrogen sources are absent or limiting. cryptococcus neoformans gat1 is an ortholog to the aspergillus nidulans area and candida albicans gat1 genes. in an attempt to define the function of this transcriptional ...201120673806
cryptococcal cellulitis in a patient with myelodysplastic syndrome. 201121103838
echinocandin and triazole antifungal susceptibility profiles for candida spp., cryptococcus neoformans, and aspergillus fumigatus: application of new clsi clinical breakpoints and epidemiologic cutoff values to characterize resistance in the sentry antimicrobial surveillance program (2009).the sentry antimicrobial surveillance program monitors global susceptibility and resistance rates for newer and established antifungal agents. the echinocandins displayed excellent potency against both candida spp. and aspergillus fumigatus in 2009 samples. using the new clinical and laboratory standards institute breakpoint values for the echinocandins when testing candida spp., we demonstrate low but measurable rates of resistance to all 3 echinocandins (anidulafungin, caspofungin, and micafun ...201121146713
first environmental isolations of cryptococcus neoformans and cryptococcus gattii in tunisia and review of published studies on environmental isolations in africa.cryptococcus neoformans and cryptococcus gattii are pathogenic yeasts that cause cryptococcosis. these fungi were commonly associated with pigeon droppings and plant materials. the habitat of these pathogens has not been yet studied in tunisia, although the ecology of these yeasts must be elucidated in order to establish surveillance programs and to prevent infections. the aim of this survey was to recover c. neoformans and c. gattii environmental isolates from pigeon droppings and plant materia ...201121197581
the rgs protein crg2 is required for establishment and progression of murine pulmonary cryptococcosis.cryptococcal regulators of g protein signaling (crg) are important for growth, differentiation, and virulence of cryptococcus neoformans. disruption of crg2 resulted in dysregulated camp signaling and attenuated virulence, whereas disruption of crg1 increased pheromone responses and enhanced virulence in the archetypal h99 strain. in tests with newly constructed near congenic mutants, a distinction between crg2δ and crg1δ gene expression was not apparent during macrophage interaction. intranasal ...201120818923
molluscum-like lesions in cryptococcal meningitis. 201120544308
[current aspects of neuromeningeal cryptococcosis in adults infected with hiv in the internal medicine service of the university hospital of treichville abidjan (cote d'ivoire)].to determine the prevalence of neuromeningeal cryptococcosis (nmc) and reporting sociodemographic, clinical, paraclinical aspects and outcome of patients.201124451495
the ubiquitin-proteasome system and f-box proteins in pathogenic fungi.the ubiquitin-proteasome system is one of the major protein turnover mechanisms that plays important roles in the regulation of a variety of cellular functions. it is composed of e1 (ubiquitin-activating enzyme), e2 (ubiquitin-conjugating enzyme), and e3 ubiquitin ligases that transfer ubiquitin to the substrates that are subjected to degradation in the 26s proteasome. the skp1, cullin, f-box protein (scf) e3 ligases are the largest e3 gene family, in which the f-box protein is the key component ...201122783111
the triple threat of cryptococcosis: it's the body site, the strain, and/or the host.cryptococcosis is the leading invasive fungal infection in the world today. over the past century, the causative agents, cryptococcus neoformans and cryptococcus gattii, have risen from the status of medical curiosities to common but life-threatening central nervous system pathogens. in an elegant experimental pathobiology study of these two organisms carried out by ngamskulrungroj et al., there are three matters that merit further discussion. first is the question of whether there is a variable ...201222782526
[quantitative real-time polymerase chain reaction for the diagnosis of invasive fungal disease].to establish the diagnostic assays of quantitative real-time polymerase chain reaction (pcr) for the diagnosis of invasive fungal disease and evaluate their accuracy in clinical samples.201222781455
using solid-state nmr to monitor the molecular consequences of cryptococcus neoformans melanization with different catecholamine precursors.melanins are a class of natural pigments associated with a wide range of biological functions, including microbial virulence, energy transduction, and protection against solar radiation. because of their insolubility and structural heterogeneity, solid-state nuclear magnetic resonance (nmr) spectroscopy provides an unprecedented means to define the molecular architecture of these enigmatic pigments. the requirement of obligatory catecholamines for melanization of the pathogenic fungus cryptococc ...201222765382
the cryptococcus neoformans capsule: a sword and a shield.the human fungal pathogen cryptococcus neoformans is characterized by its ability to induce a distinct polysaccharide capsule in response to a number of host-specific environmental stimuli. the induction of capsule is a complex biological process encompassing regulation at multiple steps, including the biosynthesis, transport, and maintenance of the polysaccharide at the cell surface. by precisely regulating the composition of its cell surface and secreted polysaccharides, c. neoformans has deve ...201222763631
comparison of primers for rapd-pcr from environmental isolates of cryptococcus neoformans, cryptococcus albidus and cryptococcus laurentii complex.various organisms have been characterized by molecular methods, including fungi of the genus cryptococcus. the purposes of this study were: to determine the discriminatory potential of the rapd (random amplified polymorphic dna) primers, the pattern of similarity of the cryptococcus species, and discuss their useful application in epidemiological studies. we analyzed 10 isolates of each specie/group: c. albidus, c. laurentii complex, c. neoformans var. grubii, all from environmental source, and ...201224031912
the link between morphotype transition and virulence in cryptococcus neoformans.cryptococcus neoformans is a ubiquitous human fungal pathogen. this pathogen can undergo morphotype transition between the yeast and the filamentous form and such morphological transition has been implicated in virulence for decades. morphotype transition is typically observed during mating, which is governed by pheromone signaling. paradoxically, components specific to the pheromone signaling pathways play no or minimal direct roles in virulence. thus, the link between morphotype transition and ...201222737071
cryptococcus neoformans yop1 , an endoplasmic reticulum curvature-stabilizing protein, participates with sey1 in influencing fluconazole-induced disomy formation.cryptococcus neoformans, an opportunistic fungal pathogen, manifests an intrinsic adaptive mechanism of resistance toward fluconazole (flc) termed heteroresistance. heteroresistance is characterized by the emergence of minor resistant subpopulations at levels of flc that are higher than the strain's minimum inhibitory concentration. the heteroresistant clones that tolerate high concentrations of flc often contain disomic chromosome 4 (chr4). sey1 , glo3 , and gcs2 on chr4 are responsible for end ...201222731401
pleiotropic effects of deubiquitinating enzyme ubp5 on growth and pathogenesis of cryptococcus neoformans.ubiquitination is a reversible protein modification that influences various cellular processes in eukaryotic cells. deubiquitinating enzymes remove ubiquitin, maintain ubiquitin homeostasis and regulate protein degradation via the ubiquitination pathway. cryptococcus neoformans is an important basidiomycete pathogen that causes life-threatening meningoencephalitis primarily in the immunocompromised population. in order to understand the possible influence deubiquitinases have on growth and virul ...201222719877
regulated expression of cyclic amp-dependent protein kinase a reveals an influence on cell size and the secretion of virulence factors in cryptococcus neoformans.cyclic amp-dependent protein kinase a (pka) regulates elaboration of the virulence factors melanin and polysaccharide capsule in cryptococcus neoformans. a mutation in pka1 encoding the catalytic subunit is known to reduce virulence in mice while a defect in pkr1 encoding the regulatory subunit enhances disease. here, we constructed strains with galactose-inducible and glucose-repressible versions of pka1 and pkr1 by inserting the gal7 promoter upstream of the genes. as expected, no capsule was ...201222717009
viral protease inhibitors affect the production of virulence factors in cryptococcus neoformans.the effects of the protease inhibitors saquinavir, darunavir, ritonavir, and indinavir on growth inhibition, protease and phospholipase activities, as well as capsule thickness of cryptococcus neoformans were investigated. viral protease inhibitors did not reduce fungal growth when tested in concentrations ranging from 0.001 to 1.000 mg/l. a tendency toward increasing phospholipase activity was observed with the highest tested drug concentration in a strain-specific pattern. however, these drugs ...201222716223
primary cutaneous cryptococcosis in brazil: report of 11 cases in immunocompetent and immunosuppressed patients.primary cutaneous cryptococcosis is an uncommon infectious disease caused by cryptococcus neoformans or cryptococcus gattii affecting immunosuppressed as well as immunocompetent patients. it is often misdiagnosed as it may mimic other cutaneous diseases.201222715820
peroxisomal and mitochondrial β-oxidation pathways influence the virulence of the pathogenic fungus cryptococcus neoformans.an understanding of the connections between metabolism and elaboration of virulence factors during host colonization by the human-pathogenic fungus cryptococcus neoformans is important for developing antifungal therapies. lipids are abundant in host tissues, and fungal pathogens in the phylum basidiomycota possess both peroxisomal and mitochondrial β-oxidation pathways to utilize this potential carbon source. in addition, lipids are important signaling molecules in both fungi and mammals. in thi ...201222707485
stimulation of cryptococcus neoformans isolated from skin lesion of aids patient matures dendritic cells and promotes hiv-1 trans-infection.dendritic cells (dcs) play a pivotal role in host defense against invaded pathogens including fungi, while dcs are targeted by fungi for deleterious regulation of the host immune response. a few studies have reported fungal modulation of dc function in these immunocompromised aids patients. cryptococcus neoformans (c. neoformans) is referred as one of the opportunistic fungi of aids. here, we isolated native c. neoformans from an aids patient and investigated its effects on dc activation and fun ...201222704932
role of ctr4 in the virulence of cryptococcus neoformans.while research has identified an important contribution for metals, such as iron, in microbial pathogenesis, the roles of other transition metals, such as copper, remain mostly unknown. recent evidence points to a requirement for copper homeostasis in the virulence of cryptococcus neoformans based on a role for a cuf1 copper regulatory factor in mouse models and in a human patient cohort. c. neoformans is an important fungal pathogen that results in an estimated 600,000 aids-related deaths yearl ...201223033470
primary cryptococcal prostatitis--rare occurrence.cryptococcosis is a well recognized infection in immunocompromised patients. cryptococcal infection primarily involves the lung and is hematogeneously spread to other organs. sometimes it might affect the genitourinary tract. the prostate gland is a rare site of primary infection due to cryptococcus neoformans. we report a case of granulomatous inflammation in the prostate as a result of crypyococcus neoformans infection in a 70 year old immunocompetent patient, a non diabetic, which was diagnos ...201223029729
identification of genes from the fungal pathogen cryptococcus neoformans related to transmigration into the central nervous system.a mouse brain transmigration assessment (mbta) was created to investigate the central nervous system (cns) pathogenesis of cryptococcal meningoencephalitis.201223028773
cryptococcal genotype influences immunologic response and human clinical outcome after meningitis.in sub-saharan africa, cryptococcal meningitis (cm) continues to be a predominant cause of aids-related mortality. understanding virulence and improving clinical treatments remain important. to characterize the role of the fungal strain genotype in clinical disease, we analyzed 140 cryptococcus isolates from 111 ugandans with aids and cm. isolates consisted of 107 nonredundant cryptococcus neoformans var. grubii strains and 8 c. neoformans var. grubii/neoformans hybrid strains. multilocus sequen ...201223015735
a paracoccidioides brasiliensis glycan shares serologic and functional properties with cryptococcal glucuronoxylomannan.the cell wall of the yeast form of the dimorphic fungus paracoccidioides brasiliensis is enriched with α1,3-glucans. in cryptococcus neoformans, α1,3-glucans interact with glucuronoxylomannan (gxm), a heteropolysaccharide that is essential for fungal virulence. in this study, we investigated the occurrence of p. brasiliensis glycans sharing properties with cryptococcal gxm. protein database searches in p. brasiliensis revealed the presence of sequences homologous to those coding for enzymes invo ...201223010152
pseudohyphal growth of cryptococcus neoformans is a reversible dimorphic transition in response to ammonium that requires amt1 and amt2 ammonium permeases.cryptococcus neoformans is a human-pathogenic basidiomycete that commonly infects hiv/aids patients to cause meningoencephalitis (7, 19). c. neoformans grows as a budding yeast during vegetative growth or as hyphae during sexual reproduction. pseudohyphal growth of c. neoformans has been observed rarely during murine and human infections but frequently during coculture with amoeba; however, the genetics underlying pseudohyphal growth are largely unknown. our studies found that c. neoformans disp ...201223002105
successful treatment of serial opportunistic infections including disseminated nocardiosis and cryptococcal meningitis in a patient with anca-associated vasculitis.we herein present a case of serial opportunistic infections that included disseminated nocardiosis and cryptococcal meningitis in a 67-year-old man who was diagnosed with anca-associated vasculitis and treated with corticosteroids. upon admission, the initial manifestations of the disease included subcutaneous tumors and multiple lesions in the brain and lungs. nocardia farcinica was identified in a culture of the aspirated pus. the patient was successfully treated for disseminated nocardiosis w ...201223124149
in good company: association between fungal glycans generates molecular complexes with unique functions.the biological properties of fungal immunogens have historically utilized testing of isolated molecules. recent findings, however, indicate that fungal glycans differing in structure and function can interact to form hybrid complexes with unique properties. in the pathogenic yeast cryptococcus neoformans, chitin-like molecules associate with capsular glucuronoxylomannan (gxm) to form functionally distinct glycan complexes. such interactions between glycans that result in the formation of structu ...201222787459
hydroxyurea treatment inhibits proliferation of cryptococcus neoformans in mice.the fungal pathogen cryptococcus neoformans (cn) is a serious threat to immunocompromised individuals, especially for hiv patients who develop meningoencephalitis. for effective cryptococcal treatment, novel antifungal drugs or innovative combination therapies are needed. recently, sphingolipids have emerged as important bioactive molecules in the regulation of microbial pathogenesis. previously we reported that the sphingolipid pathway gene, isc1, which is responsible for ceramide production, i ...201222783238
cryptococcus neoformans phospholipase b1 activates host cell rac1 for traversal across the blood-brain barrier.cryptococcus neoformans penetration into the central nervous system (cns) requires traversal of the blood-brain barrier that is composed of a single layer of human brain microvascular endothelial cells (hbmec), but the underlying mechanisms of c. neoformans traversal remain incompletely understood. c. neoformans transcytosis of hbmec monolayer involves rearrangements of the host cell actin cytoskeleton and small gtp-binding rho family proteins such as rac1 are shown to regulate host cell actin c ...201222646320
cloning of the lanosterol 14-α-demethylase ( erg11 ) gene in trichosporon asahii: a possible association between g453r amino acid substitution and azole resistance in t. asahii.lanosterol 14-α-demethylase ( erg11 protein; erg11p ), encoded by the erg11 gene, is the primary target of azoles. recently, a change in affinity of this enzyme for azoles has been reported as a resistance mechanism in several fungal species. trichosporon asahii ( t. asahii) is susceptible to fluconazole (flc). this report identified the erg11 gene of t. asahii (ncbi accession; hq176415). the erg11p of t. asahii, presumed from the dna sequence, was closely related to the erg11p of cryptococcus n ...201222621704
immune stimulating and therapeutic potential of tuftsin-incorporated nystatin liposomes against cryptococcus neoformans in leukopenic balb/c mice.cryptococcus neoformans infection is a common fungal infection in persons infected with human immune deficiency virus (hiv) or those with defective cell-mediated immunity. since treatment of cryptococcal meningitis poses a big challenge, the present study aimed to develop a novel liposomal therapeutic formulation against cryptococcosis. treatment with tuftsin-incorporated liposomes increased the anti-cryptococcal activity of murine peritoneal macrophages. prophylactic treatment of mice with tuft ...201222612788
matrix-assisted laser desorption ionization-time of flight mass spectrometry-based method for discrimination between molecular types of cryptococcus neoformans and cryptococcus gattii.we evaluated the usefulness of matrix-assisted laser desorption ionization-time of flight mass spectrometry (maldi-tof ms) for cryptococcus identification at the species and subspecies levels by using an in-house database of 25 reference cryptococcal spectra. eighty-one out of the 82 cryptococcus isolates (72 cryptococcus neoformans and 10 cryptococcus gattii) tested were correctly identified with respect to their molecular type designations. we showed that maldi-tof ms is a practicable alternat ...201222573595
the primary target organ of cryptococcus gattii is different from that of cryptococcus neoformans in a murine model.cryptococcosis is caused by the opportunistic pathogen cryptococcus neoformans or by the primary pathogen cryptococcus gattii. epidemiological studies suggest that patients infected with c. gattii mainly present with pulmonary disease, while those infected with c. neoformans commonly manifest meningoencephalitis. we compared the pathogenesis of the two species using the c. neoformans h99 and c. gattii r265 strains in a murine inhalation model. c. neoformans grew faster in the brain and caused de ...201222570277
chitin-like molecules associate with cryptococcus neoformans glucuronoxylomannan to form a glycan complex with previously unknown properties.in prior studies, we demonstrated that glucuronoxylomannan (gxm), the major capsular polysaccharide of the fungal pathogen cryptococcus neoformans, interacts with chitin oligomers at the cell wall-capsule interface. the structural determinants regulating these carbohydrate-carbohydrate interactions, as well as the functions of these structures, have remained unknown. in this study, we demonstrate that glycan complexes composed of chitooligomers and gxm are formed during fungal growth and macroph ...201222562469
role of actin-bundling protein sac6 in growth of cryptococcus neoformans at low oxygen concentration.cryptococcus neoformans, the etiologic agent of cryptococcosis, is an obligately aerobic yeast that inhabits an environmental niche exposed to ambient air. the cell doubling time was significantly prolonged under 1% o(2) relative to that under normoxic conditions. no apparent cell cycle arrest occurred following a shift from ambient air to 1% o(2). however, yeast cells became hypersensitive to the actin monomer-sequestering agent latrunculin a at 1% o(2), indicating that proper actin function is ...201222562467
vaccine potential of cytosolic proteins loaded fibrin microspheres of cryptococcus neoformans in balb/c mice.cryptococcosis is a leading mycological cause of mortality among immunologically compromised individuals. in order to develop an effective vaccine against cryptococcus neoformans, the cytosolic proteins (cp) of the pathogen have been used as an antigen in combination with different formulations. in the present study, we have demonstrated that cp encapsulated poly-lactide co-glycolide (plga) microsphere further co-encapsulated into the biocompatible fibrin cross-linked plasma beads (fib-plga-cp) ...201222553959
surfactant protein d facilitates cryptococcus neoformans infection.concurrent with the global escalation of the aids pandemic, cryptococcal infections are increasing and are of significant medical importance. furthermore, cryptococcus neoformans has become a primary human pathogen, causing infection in seemingly healthy individuals. although numerous studies have elucidated the virulence properties of c. neoformans, less is understood regarding lung host immune factors during early stages of fungal infection. based on our previous studies documenting that pulmo ...201222547543
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