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[a case of pulmonary cryptococcus neoformans infection]. 201223257048
[pattern recognition and host defense response to cryptococcus neoformans].cryptococcus neoformans is an opportunistic fungal pathogen that causes fatal meningoencephalitis in immunocompromised hosts such as patients with aids and hematological malignancy. host defense to c. neoformans infection is mediated by th1-type cellular immunity, which is triggered by host cell recognition of the pathogen-associated molecular patterns via the pattern recognition receptors. recently, our study revealed that tlr9-dependent sensing of cryptococcal dna was a pivotal step in initiat ...201223257725
cryptococcus neoformans growth and protection from innate immunity are dependent on expression of a virulence-associated dead-box protein, vad1.the fungus cryptococcus neoformans has emerged as a major cause of meningoencephalitis worldwide. host response to the fungus involves both innate and adaptive immunity, but fungal genes that modulate these processes are poorly understood. previous studies demonstrated attenuated virulence of a mutant of a virulence-associated dead-box protein (vad1) in mice, despite normal growth at host temperatures, suggesting modulation of the immune response. in the present study, the δvad1 mutant demonstra ...201223264050
toxoplasma gondii: the effect of fluconazole combined with sulfadiazine and pyrimethamine against acute toxoplasmosis in murine model.toxoplasma gondii is an important opportunistic pathogen for immunocompromised patients and responsible for toxoplasmic encephalitis, which is often lethal. treatment for this infection is limited to a restricted therapeutic arsenal. in this work we tested the combination of fluconazole with the current treatment for acute toxoplasmosis on the murine model in vivo. different experimental groups were treated with combinations of sulfadiazine plus pyrimethamine with fluconazole and pyrimethamine w ...201223270807
structural and functional studies on a proline-rich peptide isolated from swine saliva endowed with antifungal activity towards cryptococcus neoformans.a proline-rich peptide of 2733da, isolated from pig parotid granule preparations was tested against different pathogenic fungi. it showed interesting antifungal activity towards a clinical isolate of cryptococcus neoformans, with an ec(50) of 2.2μm. neither cytotoxic nor haemolytic effects were observed towards mammalian cells. circular dichroism and infrared spectroscopic studies showed that the peptide adopted a combination of polyproline type-ii, β-turn and unordered conformations at physiolo ...201223274276
isolated skull cryptococcosis in an immunocompetent patient.a 62-year-old immunocompetent rural woman who represents an isolated cryptococcal skull infection without systematic involvement is described. diagnosis was based on positive india ink staining, positive histopathologic examination, and positive culture. species identification was performed by growth on sabouraud dextrose agar and chromagar medium and by sequencing of the intergenic and internal transcribed spacer regions of the rrna genes. this case describes a rare presentation of cryptococcus ...201223275242
[cryptococcus neoformans meningitis in children and adolescents infected with hiv].three cases of meningitis due to criptococcus in children infected with hiv are reported. all patients had severe immunodeficiency. the first case occurred before antiretroviral therapy. the second case had poor adherence to treatment. the third case is a teenager with prolonged fever, who did not have a clear source of transmission of hiv and was immunodeficient at the time of diagnosis. examination of cerebrospinal fluid with india ink dye was essential for making the diagnosis in all three ca ...201223282503
molecular epidemiology of italian clinical cryptococcus neoformans var. grubii isolates.cryptococcus neoformans variety grubii is the major etiological agent of cryptococcal meningitis in both immunocompromised and immunocompetent patients. the current pcr-based molecular methods are not sufficient to discriminate among the different populations of this yeast. therefore, the aim of the present study was to investigate the genotypes of the italian clinical c. neoformans var. grubii isolates by multilocus sequence typing (mlst). a total of 53 isolates, each representative of a single ...201323286351
microscopic detection of yeasts using fluorescence in situ hybridization.fluorescence in situ hybridization (fish) has been widely used for the detection and identification of microorganisms in their natural environments. in this chapter we describe the use of a simple fish-based protocol to detect and identify clinically relevant yeast species in culture and biological samples using cryptococcus neoformans as a model. after fixation of cells with paraformaldehyde, the same are embedded in hybridization buffer containing specific fluorochrome-labeled oligonucleotide ...201323296886
approaching the functional annotation of fungal virulence factors using cross-species genetic interaction profiling.in many human fungal pathogens, genes required for disease remain largely unannotated, limiting the impact of virulence gene discovery efforts. we tested the utility of a cross-species genetic interaction profiling approach to obtain clues to the molecular function of unannotated pathogenicity factors in the human pathogen cryptococcus neoformans. this approach involves expression of c. neoformans genes of interest in each member of the saccharomyces cerevisiae gene deletion library, quantificat ...201223300468
identification and functional demonstration of mirnas in the fungus cryptococcus neoformans.micrornas (mirnas), endogenous posttranscriptional repressors by base-pairing of their cognate mrnas in plants and animals, have mostly been thought lost in the kingdom of fungi. here, we report the identification of mirnas from the fungus cryptococcus neoformans. with bioinformatics and northern blotting approaches, we found that these mirnas and their hairpin precursors were present in this fungus. the size of mir1 and mir2 is 22 nt and 18 nt, respectively. the precursors are about ∼70 nt in l ...201223300755
the microbial capsular polysaccharide galactoxylomannan inhibits il-17a production in circulating t cells from rheumatoid arthritis patients.the persistence of activated t cells in rheumatoid arthritis (ra) synovium may be attributable to increased homing, increased retention or a possible imbalance between cell proliferation and programmed cell death. induction of apoptosis may represent a potential therapeutic approach. galactoxylomannan (galxm) from the opportunistic fungus cryptococcus neoformans can interact with t cells and induce t-cell apoptosis through the inhibition of cd45 phosphatase activity. the aim of this study was to ...201323308194
evaluation of the anticryptococcal activity of the antibiotic polymyxin b in vitro and in vivo.polymyxin b (pmb), a cationic lipid oligopeptide used to treat gram-negative bacterial infections, was previously identified to possess broad-spectrum antifungal activity and to work synergistically with azole antifungals in vitro. here we evaluated the efficacy of pmb against cryptococcus neoformans in vitro and in vivo and explored the mechanism of the hypersensitivity of this fungus to this compound. using comparative time-course assays, pmb was found to kill both proliferative and quiescent ...201323313397
cryptococcus neoformans rim101 is associated with cell wall remodeling and evasion of the host immune responses.infectious microorganisms often play a role in modulating the immune responses of their infected hosts. we demonstrate that cryptococcus neoformans signals through the rim101 transcription factor to regulate cell wall composition and the host-pathogen interface. in the absence of rim101, c. neoformans exhibits an altered cell surface in response to host signals, generating an excessive and ineffective immune response that results in accelerated host death. this host immune response to the rim101 ...201323322637
the mannoprotein cig1 supports iron acquisition from heme and virulence in the pathogenic fungus cryptococcus neoformans.iron acquisition is critical for virulence of the human pathogenic fungus cryptococcus neoformans. the cryptococcal transcript for the extracellular mannoprotein cig1 is highly regulated by iron and abundant in iron-starved cells, suggesting a role in iron acquisition. indeed, loss of cig1 resulted in delayed growth on heme at physiological ph. expression of cig1 is regulated by the ph-responsive transcription factor rim101, and loss of rim101 also impaired growth on heme. a cig1δ mutant was les ...201323322859
epidemiology of opportunistic invasive fungal infections in china: review of literature.to summarize the recent findings on the epidemiology of medically important, opportunistic invasive fungal infections (ifis) in china and discuss the relevant social, economical reasons and medical factors.201323324290
disseminated cryptococcosis presenting as cellulitis in a renal transplant recipient.cellulitis is an unusual presentation of cryptococcal infection in renal allograft recipients. in such patients, disseminated cryptococcal infection can result in significant morbidity and mortality. patients are often treated with antibiotics before a definitive diagnosis is made, delaying appropriate therapy. we describe the case of a 43-year-old post renal transplant recipient presenting with fever and swelling in the right thigh. on physical examination, the patient was found to have feature ...201323324822
two rare cases of central nervous system opportunistic mycoses.this article presents two cases of opportunistic mycoses (oms) of the central nervous system (cns) caused by cryptococcus neoformans and aspergillus nidulans, respectively. the patients were hospitalised in local hospitals between 2009 and 2011 because of unspecific symptoms (fever, headache, and/or weight lost). duration of symptoms varied from 4 days to over 2 weeks. the patients were treated with antibiotics and symptomatically. om was not suspected in any of them. the patients became critica ...201223334046
disseminated cryptococcosis initially presenting as cellulitis in a patient suffering from nephrotic syndrome.cryptococcosis is considered as an opportunistic infection because it mainly occurs in immunosuppressed hosts. c. neoformans is usually acquired by the respiratory route and then may disseminate hematogenously to other places, such as meninges, bone and skin. cutaneous involvement is a rare but important feature of disseminated cryptococcosis with a poor outcome if misdiagnosis. we reported the first case of patients with nephrotic syndrome suffering from disseminated cryptococcosis initially pr ...201323336386
altered immune response differentially enhances susceptibility to cryptococcus neoformans and cryptococcus gattii infection in mice expressing the hiv-1 transgene.cryptococcus neoformans var. grubii is the most frequent cause of aids-associated cryptococcosis worldwide, while cryptococcus gattii usually infects immunocompetent people. to understand the mechanisms which cause differential susceptibility to these cryptococcal species in hiv infection, we established and characterized a model of cryptococcosis in cd4c/hiv(muta) transgenic (tg) mice expressing gene products of hiv-1 and developing an aids-like disease. tg mice infected intranasally with c. ne ...201323340313
genomic insights into the atopic eczema-associated skin commensal yeast malassezia sympodialis.malassezia commensal yeasts are associated with a number of skin disorders, such as atopic eczema/dermatitis and dandruff, and they also can cause systemic infections. here we describe the 7.67-mbp genome of malassezia sympodialis, a species associated with atopic eczema, and contrast its genome repertoire with that of malassezia globosa, associated with dandruff, as well as those of other closely related fungi. ninety percent of the predicted m. sympodialis protein coding genes were experimenta ...201323341551
susceptibility profile of clinical and environmental isolates of cryptococcus neoformans and cryptococcus gattii in uberaba, minas gerais, brazil.cryptococcus neoformans and c. gattii are the etiologic agents of cryptococcosis, a life-threatening disease in both immunocompromised and immunocompetent hosts. antifungal resistance has been evaluated using different methods, breakpoints, and sizes of test populations and it is an emerging as a significant issue worldwide. a total of 176 (95 clinical and 81 environmental) c. neoformans and eight clinical c. gattii isolates were evaluated to determine the minimal inhibitory concentration (mic) ...201323343452
effect of virulence factors on the photodynamic inactivation of cryptococcus neoformans.opportunistic fungal pathogens may cause an array of superficial infections or serious invasive infections, especially in immunocompromised patients. cryptococcus neoformans is a pathogen causing cryptococcosis in hiv/aids patients, but treatment is limited due to the relative lack of potent antifungal agents. photodynamic inactivation (pdi) uses the combination of non-toxic dyes called photosensitizers and harmless visible light, which produces singlet oxygen and other reactive oxygen species t ...201323349872
deafness and blindness in a renal transplant recipient with cryptococcal meningitis.infections are a major determinant of outcome in kidney transplantation. opportunistic pathogens are common in kidney recipients and several organs can be affected. central nervous system infection in transplant recipients is a medical emergency. there is limited information in the literature concerning post-transplantation cryptococcal infection. deafness and blindness are not classic findings. we report a case of meningocerebral cryptococcosis complicated by deafness and blindness after kidney ...201323354195
determination of chitin content in fungal cell wall: an alternative flow cytometric method.the conventional methods used to evaluate chitin content in fungi, such as biochemical assessment of glucosamine release after acid hydrolysis or epifluorescence microscopy, are low throughput, laborious, time-consuming, and cannot evaluate a large number of cells. we developed a flow cytometric assay, efficient, and fast, based on calcofluor white staining to measure chitin content in yeast cells. a staining index was defined, its value was directly related to chitin amount and taking into cons ...201323359335
early versus delayed antiretroviral therapy and cerebrospinal fluid fungal clearance in adults with hiv and cryptococcal meningitis.the burden of cryptococcus neoformans in cerebrospinal fluid (csf) predicts clinical outcomes in human immunodeficiency virus (hiv)-associated cryptococcal meningitis (cm) and is lower in patients on antiretroviral therapy (art). this study tested the hypothesis that initiation of art during initial treatment of hiv/cm would improve csf clearance of c. neoformans.201323362285
the antimicrobial activities of extract and compounds isolated from brillantaisia lamium.background:brillantaisia lamium is an erect branched herb, which grows to a height of 1.50 m in moist tropical areas, both in full sun and partial shade. in , the aerial part of this plant is used in the treatment of various microbial infections such as skin diseases and infections of urinary tract. the aim of this study was to evaluate the antimicrobial activities of ch(2)cl(2): meoh (1:1) extract, fractions and compounds from the aerial part of b. lamium.methods: the plant was dried and extrac ...201123365474
[cryptococcal osteomyelitis in a patient with a lymphocytic leukemia treated with fludarabine-cyclophosphamide-rituximab].cryptococcosis is a serious invasive fungal infection mostly described in patients with cell-mediated immunosuppression. cryptococcus neoformans osteomyelitis is a rare infection that occurs mainly during disseminated forms.201323375857
sex-induced silencing operates during opposite-sex and unisexual reproduction in cryptococcus neoformans.cryptococcus neoformans is a human fungal pathogen that undergoes a dimorphic transition from yeast to hyphae during a-α opposite-sex mating and α-α unisexual reproduction (same-sex mating). infectious spores are generated during both processes. we previously identified a sex-induced silencing (sis) pathway in the c. neoformans serotype a var. grubii lineage, in which tandem transgene arrays trigger rnai-dependent gene silencing at a high frequency during a-α opposite-sex mating, but at an ∼250- ...201323378067
ploidy variation as an adaptive mechanism in human pathogenic fungi.changes in ploidy have a profound and usually negative influence on cellular viability and proliferation, yet the vast majority of cancers and tumours exhibit an aneuploid karyotype. whether this genomic plasticity is a cause or consequence of malignant transformation remains uncertain. systemic fungal pathogens regularly develop aneuploidies in a similar manner during human infection, often far in excess of the natural rate of chromosome nondisjunction. as both processes fundamentally represent ...201323380396
clinical experience in invasive fungal infections: multiple fungal infection as the first presentation of hiv.fungal infections constitute an important cause of morbidity and mortality in hiv-infected patients. the authors describe the case of a 40-year-old healthy male patient with a 2-month history of fever, shivers, asthenia and anorexia, who had lost weight during the past 6 months. laboratory investigations revealed a positive hiv screening. computed tomography scans of the chest and abdomen showed thoracic and lumbo-aortic adenopathies. cryptococcus neoformans was isolated from cultures of blood, ...201323381983
fungal meningitis in an immunocompetent patient.cryptococcal meningitis is a rare entity among immunocompetent hosts but, when it occurs, it is associated with significant morbidity and mortality. clinical presentation as well as the course of the disease is usually subtle and indolent with headache and altered mental status. the authors present the case of a 59-year-old man, who sought medical help with a 2-week history of headaches accompanied by nausea and visual and hearing disturbances. on admission the patient was afebrile, presented vi ...201323381985
phospholipase c of cryptococcus neoformans regulates homeostasis and virulence by providing inositol trisphosphate as a substrate for arg1 kinase.phospholipase c (plc) of cryptococcus neoformans (cnplc1) is crucial for virulence of this fungal pathogen. to investigate the mechanism of cnplc1-mediated signaling, we established that phosphatidylinositol 4,5-bisphosphate (pip(2)) is a major cnplc1 substrate, which is hydrolyzed to produce inositol trisphosphate (ip(3)). in saccharomyces cerevisiae, plc1-derived ip(3) is a substrate for the inositol polyphosphate kinase arg82, which converts ip(3) to more complex inositol polyphosphates. in t ...201323381992
global transcriptome profile of cryptococcus neoformans during exposure to hydrogen peroxide induced oxidative stress.the ability of the opportunistic fungal pathogen cryptococcus neoformans to resist oxidative stress is one of its most important virulence related traits. to cope with the deleterious effect of cellular damage caused by the oxidative burst inside the macrophages, c. neoformans has developed multilayered redundant molecular responses to neutralize the stress, to repair the damage and to eventually grow inside the hostile environment of the phagosome. we used microarray analysis of cells treated w ...201323383070
not all that shines is cancer: pulmonary cryptococcosis mimicking lymphoma in [(18)] f fluoro-2-deoxy-d-glucose positron emission tomography.we report of a case of pulmonary cryptococcosis mimicking lymphoma in a positron emission tomography (fdg-pet) scan. a 62-year old man with diffuse large b-cell lymphoma had complete resolution of abdominal and pulmonary lesions after three cycles of rituximab-based chemotherapy (r-chop). however, fdg-pet showed new pulmonary nodules, suggesting active lymphoma. chronic inflammatory granuloma was seen in the histopathological exam, with round-shaped structures compatible with fungus, later ident ...201223386093
environmental predictors and incubation period of aids-associated penicillium marneffei infection in ho chi minh city, vietnam.penicillium marneffei is an emerging dimorphic mycosis endemic in southeast asia, and a leading cause of mortality among human immunodeficiency virus (hiv)-infected people in the region. factors governing the seasonal incidence of p. marneffei infection are unknown, and may yield critical insights into possible reservoirs or modes of acquisition.201323386634
[cryptococcal meningitis in a patient with a ventriculoperitoneal shunt and monitoring for pulmonary sarcoidosis].the fungus cryptococcus neoformans can cause common opportunistic infection in acquired immune deficiency syndrome (aids) patients. but other conditions can be associated with sarcoidosis. meningoencephalitis is the most common manifestation of this disease. one of the most important neurological complications is the development of intracranial hypertension (ich), which may result in high morbidity and mortality. we report the case of a patient harboring a ventriculoperitoneal shunt, and having ...201323395187
unusual galactofuranose modification of a capsule polysaccharide in the pathogenic yeast cryptococcus neoformans.galactofuranose (galf) is the five-membered ring form of galactose. although it is absent from mammalian glycans, it occurs as a structural and antigenic component of important cell surface molecules in a variety of microbes, ranging from bacteria to parasites and fungi. one such organism is cryptococcus neoformans, a pathogenic yeast that causes lethal meningoencephalitis in immunocompromised individuals, particularly aids patients. c. neoformans is unique among fungal pathogens in bearing a co ...201323408430
bacterial and fungal meningitis and antimicrobial susceptibility pattern in tikur anbessa university hospital, addis ababa, ethiopia.meningitis is usually caused by viral, bacterial or fungal pathogens. bacterial meningitis is a medical emergency and if untreated has a high mortality rate. even among those who survive the infection, some may develop permanent neurological disorders.201123409400
stalled spliceosomes are a signal for rnai-mediated genome defense.using the yeast cryptococcus neoformans, we describe a mechanism by which transposons are initially targeted for rnai-mediated genome defense. we show that intron-containing mrna precursors template sirna synthesis. we identify a spliceosome-coupled and nuclear rnai (scanr) complex required for sirna synthesis and demonstrate that it physically associates with the spliceosome. we find that rnai target transcripts are distinguished by suboptimal introns and abnormally high occupancy on spliceosom ...201323415457
fungal cell wall organization and biosynthesis.the composition and organization of the cell walls from saccharomyces cerevisiae, candida albicans, aspergillus fumigatus, schizosaccharomyces pombe, neurospora crassa, and cryptococcus neoformans are compared and contrasted. these cell walls contain chitin, chitosan, β-1,3-glucan, β-1,6-glucan, mixed β-1,3-/β-1,4-glucan, α-1,3-glucan, melanin, and glycoproteins as major constituents. a comparison of these cell walls shows that there is a great deal of variability in fungal cell wall composition ...201323419716
[recognition of intact cells from cryptococcus neoformans by the anti-glucuronoxylomannan 4b3 monoclonal antibody].the capacity of the 4b3 monoclonal antibody, previously obtained by immunization of balb/c mice with the capsular polysaccharide of cryptococcus neoformans was studied to recognize this structure as part of the intact cell of this yeast. with this aim, 4b3 was evaluated by cellular elisa and indirect immunofluorescence, using as an antigen a cell suspension of the 028 lmipk c. neoformans strain. serum from the mouse used in the fusion for obtaining 4b3 monoclonal antibody was used as a positive ...201323427436
determination of epidemiology of clinically isolated cryptococcus neoformans strains in japan by multilocus sequence typing.cryptococcus neoformans and cryptococcus gattii are the causative agents of cryptococcosis. despite its importance, our knowledge of the epidemiology of cryptococcosis in japan remains limited. to establish an epidemiological database on cryptococcosis in japan, we determined the genetic variability of 44 japanese clinical isolates of c. neoformans (var. grubii: serotype a) by multilocus sequence typing (mlst). the strains were clinically isolated from 1992 to 2011 in 5 different areas of japan ...201323429086
susceptibility of intact germinating arabidopsis thaliana to human fungal pathogens cryptococcus neoformans and c. gattii.the fungus cryptococcus contributes a large global burden of infectious death in both hiv-infected and healthy individuals. as cryptococcus is an opportunistic pathogen, much of the evolutionary pressure shaping virulence occurs in environments in contact with plants and soil. the present studies investigated inoculation of intact seeds of the common weed arabidopsis thaliana with fungal cells over a 21-day period. c. gattii was the more virulent plant pathogen, resulting in disrupted germinatio ...201323435895
[presumptive identification of cryptococcus gattii isolated from terminalia catappa in montería city, córdoba, colombia].the members of the cryptococcus neoformans species complex are responsible for cryptococcosis in animals and humans. human infection is thought to be acquired by inhalation of airborne propagules from an environmental source; therefore it is greatly important to study their habitat. objective: to determine the ecological relationship of cryptococcus gattii with terminalia catappa trees present in urban areas of montería city in colombia.201123437518
[effect of 4b3 monoclonal antibody on the experimental cryptococcus neoformans infection].frequent relapses and high lethality of criptococcosis has encouraged the search for new therapeutic strategies.201123437519
biological activities of α-pinene and β-pinene enantiomers.the antimicrobial activities of the isomers and enantiomers of pinene were evaluated against bacterial and fungal cells. the agar diffusion test showed that only the positive enantiomers of the a- and β-isomers of pinene were active. the minimal inhibitory concentration (mic) and minimal microbicidal concentration (mmc) of these monoterpenes were also determined, confirming that the positive enantiomers exhibited microbicidal activity against all fungi and bacteria tested with mics ranging from ...201223442885
calcineurin governs thermotolerance and virulence of cryptococcus gattii.the pathogenic yeast cryptococcus gattii, which is causing an outbreak in the pacific northwest region of north america, causes life-threatening pulmonary infections and meningoencephalitis in healthy individuals, unlike cryptococcus neoformans, which commonly infects immunocompromised patients. in addition to a greater predilection for c. gattii to infect healthy hosts, the c. gattii genome sequence project revealed extensive chromosomal rearrangements compared with c. neoformans, showing genom ...201323450261
quit stalling or you'll be silenced.the use of small rnas to program gene regulation and genome defense necessitates ever-changing choices about the sequences used for small-rna biogenesis. dumesic et al. now reveal stalled spliceosomes as a trigger for small-rna biogenesis in the pathogenic fungus cryptococcus neoformans.201323452843
[clinical problems in medical mycology: problem number 46].a 49 year old-man, without known previous diseases, who suffered an acute lung infection, is presented. he was a smoker and belonged to a high socioeconomic class. he suddenly presented high fever, dry cough and legs' pain. thorax x-ray and ct scan showed two excavated pneumonic infiltrates in the lower part of the right lung. he was treated with antibacterial antibiotics without clinical response. a transparietal fine needle lung biopsy was performed and the histopathology and cytological studi ...201423462234
[apoptosis-like cell death of cryptococcus neoformans mediated by staphylococcus aureus contact].co-culture of the fungal pathogen cryptococcus neoformans with staphylococcus aureus results in the death of the fungus, caused by the adherence to the latter. the present study found that the molecules responsible for this adherence were capsular glucuronoxylomannan (gxm) (present on c. neoformans) and a glycolytic enzyme triosephosphate isomerase (tpi) (present on s. aureus). the mannan backbone of gxm and purified tpi interacted in vitro. gxm-bound tpi molecules were identified by immunoelect ...201323470955
ustilago maydis phosphodiesterases play a role in the dimorphic switch and in pathogenicity.components of the camp (cyclic amp) signalling cascades are conserved from fungi to humans, and are particularly important for fungal dimorphism and pathogenicity. previous work has described two phosphodiesterases, umpde1 and umpde2, in ustilago maydis which show strong phosphodiesterase activity. we further characterized the biological function(s) of these phosphodiesterases in u. maydis. specifically, we examined their possible role(s) in regulation of the camp-dependent protein kinase a (pka ...201323475947
essential roles of the kar2/bip molecular chaperone downstream of the upr pathway in cryptococcus neoformans.the endoplasmic reticulum (er) is a central hub where secreted or membrane-bound proteins are maturated and folded properly in eukaryotes. maintenance of er homeostasis is particularly important for human fungal pathogens, such as cryptococcus neoformans, which encounter a plethora of host-mediated stresses during infection. our previous study demonstrated that the unfolded protein response (upr) pathway, composed of the evolutionarily conserved ire1 kinase and the unique hxl1 transcription fact ...201323484059
advancing translational immunology in hiv-associated cryptococcal meningitis. 201323493727
the phenotype of the cryptococcus-specific cd4+ memory t-cell response is associated with disease severity and outcome in hiv-associated cryptococcal meningitis.correlates of immune protection in patients with human immunodeficiency virus (hiv)-associated cryptococcal meningitis are poorly defined. a clearer understanding of these immune responses is essential to inform rational development of immunotherapies.201323493728
cryptococcus neoformans copper detoxification machinery is critical for fungal virulence.copper (cu) is an essential metal that is toxic at high concentrations. thus, pathogens often rely on host cu for growth, but host cells can hyperaccumulate cu to exert antimicrobial effects. the human fungal pathogen cryptococcus neoformans encodes many cu-responsive genes, but their role in infection is unclear. we determined that pulmonary c. neoformans infection results in cu-specific induction of genes encoding the cu-detoxifying metallothionein (cmt) proteins. mutant strains lacking cmts o ...201323498952
synthesis, bioevaluation and structural study of substituted phthalazin-1(2h)-ones acting as antifungal agents.twenty-five polysubstituted phthalazinone derivatives were synthesized and tested for their antifungal activity against a panel of pathogenic and clinically important yeasts and filamentous fungi. among them, the compound 4-(4-chlorobenzyl)-2-methylphthalazin-1(2h)-one (5) exhibited a remarkable antifungal activity against standardised strains of dermatophytes and cryptococcus neoformans, as well as against some clinical isolates. a physicochemical study performed on compound 5 revealed its conf ...201323507777
pichia fabianii blood infection in a premature infant in china: case report.invasive fungal infections caused by uncommon fungi have increased in recent years. hospitalized low-birth-weight infants are at high risk for neonatal fungal infections. pichia fabianii is a rare pathogen causing blood infection, which has reportedly caused only 4 cases of fungemia and 1 case of endocarditis worldwide. here, we describe the first case of a p. fabianii blood infection in a premature infant in china.201323510524
a copper hyperaccumulation phenotype correlates with pathogenesis in cryptococcus neoformans.cryptococcus neoformans is a major human pathogen and a cause of meningoencephalitis in immunocompromised patients. many factors contribute to the extraordinary survivability and pathogenicity of this fungus in humans, including copper homeostasis pathways. previous work has shown that deletion of the copper-dependent regulator cuf1 results in decreased virulence and dissemination in brain infection, suggesting that copper acquisition is important to the persistence of this pathogen. here, we sh ...201323511945
discovery of 3,3'-diindolylmethanes as potent antileishmanial agents.an efficient protocol for synthesis of 3,3'-diindolylmethanes using recyclable fe-pillared interlayered clay (fe-pilc) catalyst under aqueous medium has been developed. all synthesized 3,3'-diindolylmethanes showed promising antileishmanial activity against leishmania donovani promastigotes as well as axenic amastigotes. structure-activity relationship analysis revealed that nitroaryl substituted diindolylmethanes showed potent antileishmanial activity. the 4-nitrophenyl linked 3,3'-diindolylmet ...201323517732
antifungal activity, sar and physicochemical correlation of some thiazole-1,3,5-triazine derivatives.present research communication was towards the investigation of antifungal minimum inhibitory concentration (mic) and minimum fingicidal concentration (mfc) activity of some substituted clubbed thiazole-1,3,5-triazines derivatives and effect of physicochemical properties on bioactivity.201223518015
epidemiology and molecular characterization of cryptococcus neoformans isolated from pigeon excreta in mazandaran province, northern iran.the aims of this study were to verify the presence of cryptococcus neoformans in pigeon excreta in mazandaran province, iran, to identify the varieties of the c. neoformans isolates using d1/d2 and igs sequencing, and determining the presence of the two mating types: α and a.201223518018
in vitro antifungal activities of amphotericin b, 5-fluorocytosine, fluconazole and itraconazole against cryptococcus neoformans isolated from cerebrospinal fluid and blood from patients in serbia.recently, geographic variations in resistance to agents commonly used in the treatment of cryptococcosis have been reported. therefore, the antifungal susceptibilities of 31 clinical isolates of cryptococcus neoformans, collected in serbia during 10-year period, were investigated. strains were isolated from cerebrospinal fluid (n=28) and blood (n=3), from patients with aids (n=26), lymphoma (n=4) and kidney transplant recipient (n=1). the minimal inhibitory concentrations (mics) of amphotericin ...201223518082
seasonal prevalence of cryptococcus neoformans var. grubii and cryptococcus gattii inhabiting eucalyptus terreticornis and eucalyptus camaldulensis trees in jabalpur city of madhya pradesh, central india.this study presents a two-year retrospective analysis of the work done during 2003-2005 on the distribution population density and isolation frequency of cryptococcus neoformans var. grubii and cryptococcus gattii recovered from different parts of eucalyptus tree spp., at jabalpur madhya pradesh, central india. of the 1000 samples collected from bark, flowers, fruits, buds and leaves of eucalyptus trees e. terreticornis and e. camaldulensis, 32 (3.2%) were found to be positive for c.n var. grubi ...201223518169
molecular and genetic evidence for a tetrapolar mating system in the basidiomycetous yeast kwoniella mangrovensis and two novel sibling species.kwoniella mangrovensis has been described as a sexual species with a bipolar mating system. phylogenetic analysis of multiple genes places this species together with kwoniella heveanensis in the kwoniella clade, a sister clade to that containing two pathogenic species of global importance, cryptococcus neoformans and cryptococcus gattii, within the tremellales. recent studies defining the mating type loci (mat) of species in these clades showed that, with the exception of c. neoformans and c. ga ...201323524993
the transcriptional response of cryptococcus neoformans to ingestion by acanthamoeba castellanii and macrophages provides insights into the evolutionary adaptation to the mammalian host.virulence of cryptococcus neoformans for mammals, and in particular its intracellular style, was proposed to emerge from evolutionary pressures on its natural environment by protozoan predation, which promoted the selection of strategies that allow intracellular survival in macrophages. in fact, acanthamoeba castellanii ingests yeast cells, which then can replicate intracellularly. in addition, most fungal factors needed to establish infection in the mammalian host are also important for surviva ...201323524994
methamphetamine alters blood brain barrier protein expression in mice, facilitating central nervous system infection by neurotropic cryptococcus neoformans.methamphetamine (meth) is a drug of abuse that is a potent and highly addictive central nervous system (cns) stimulant. the blood brain barrier (bbb) is a unique interface that in part functions to prevent microbial invasion of the cns. the effects of meth on brain vasculature have not been studied extensively. we hypothesized that meth alters the bbb integrity, increasing susceptibility to cns infection. using a murine model of meth administration, we demonstrated that meth alters bbb integrity ...201323532099
abrogation of il-4 receptor-α-dependent alternatively activated macrophages is sufficient to confer resistance against pulmonary cryptococcosis despite an ongoing t(h)2 response.in the murine model of pulmonary infection with cryptococcus neoformans, il-4 receptor α (il-4rα)-dependent polyfunctional t(h)2 cells induce disease progression associated with alternative activation of lung macrophages. to characterize the effector role of il-4rα-dependent alternatively activated macrophages (aamph), we intra-nasally infected mice with genetically ablated il-4rα expression on macrophages (lysm(cre)il-4rα(-/lox) mice) and il-4rα(-/lox) littermates. lysm(cre)il-4rα(-/lox) mice w ...201323532373
development of a singleplex pcr assay for rapid identification and differentiation of cryptococcus neoformans var. grubii, cryptococcus neoformans var. neoformans, cryptococcus gattii, and hybrids.a singleplex pcr assay using a single primer pair targeting the putative sugar transporter gene was developed here to distinguish cryptococcus neoformans var. grubii, cryptococcus neoformans var. neoformans, and cryptococcus gattii according to the distinct size of the amplicon. the interspecies and intravarietal hybrids were also characterized on the basis of distinct combined profiles of amplicons. this pcr assay is a rapid, simple, and reliable approach suitable for laboratory diagnoses and l ...201323536400
3-bromopyruvate: a novel antifungal agent against the human pathogen cryptococcus neoformans.we have investigated the antifungal activity of the pyruvic acid analogue: 3-bromopyruvate (3-bp). growth inhibition by 3-bp of 110 strains of yeast-like and filamentous fungi was tested by standard spot tests or microdilution method. the human pathogen cryptococcus neoformans exhibited a low minimal inhibitory concentration (mic) of 0.12-0.15 mm 3-bp. the high toxicity of 3-bp toward c. neoformans correlated with high intracellular accumulation of 3-bp and also with low levels of intracellular ...201323541578
prevalence and outcomes of cryptococcal antigenemia in hiv-seropositive patients hospitalized for suspected tuberculosis in uganda.cryptococcal infection occurs in hiv-seropositive patients and is associated with high mortality. however, limited information is available on the prevalence and outcomes of cryptococcal antigenemia among hospitalized hiv-seropositive patients in sub-saharan africa.201323542636
caulerprenylols a and b, two rare antifungal prenylated para-xylenes from the green alga caulerpa racemosa.two new prenylated para-xylenes, named caulerprenylols a (1) and b (2), were isolated from the green alga caulerpa racemosa, collected from the zhanjiang coastline, china. the structures of the two metabolites were elucidated on the basis of detailed spectroscopic analysis. this is the first report of prenylated para-xylenes from marine algae and from marine organisms as well. moreover, caulerprenylol b (2) is also characterized by an uncommon indane ring system. in in vitro bioassays, the new c ...201323548547
comparative genomics of serial isolates of cryptococcus neoformans reveals gene associated with carbon utilization and virulence.the opportunistic fungal pathogen cryptococcus neoformans is a leading cause of mortality among the human immunodeficiency virus/acquired immunodeficiency syndrome population and is known for frequently causing life-threatening relapses. to investigate the potential contribution of in-host microevolution to persistence and relapse, we have analyzed two serial isolates obtained from a patient with acquired immunodeficiency syndrome who suffered an initial and relapse episode of cryptococcal menin ...201323550133
the copper interference with the melanogenesis of cryptococcus neoformans.melanin is a pigment produced by laccase, a phenoloxydase enzyme, and is related to the virulence of cryptococcus neoformans as it is also considered an adaption mechanism to environmental conditions and protection against uv radiation, phagocytic system attack and antifungal drugs. laccase synthesis is stimulated by several factors, including copper metabolism. the current study shows c. neoformans strains with higher melanization intensity when grown in l-dopa medium supplemented with differen ...201323563765
reactive oxygen species homeostasis and virulence of the fungal pathogen cryptococcus neoformans requires an intact proline catabolism pathway.degradation of the multifunctional amino acid proline is associated with mitochondrial oxidative respiration. the two-step oxidation of proline is catalyzed by proline oxidase and δ(1)-pyrroline-5-carboxylate (p5c) dehydrogenase, which produce p5c and glutamate, respectively. in animal and plant cells, impairment of p5c dehydrogenase activity results in p5c-proline cycling when exogenous proline is supplied via the actions of proline oxidase and p5c reductase (the enzyme that converts p5c to pro ...201323564202
allergen1 regulates polysaccharide structure in cryptococcus neoformans.cryptococcus neoformans is an important human, fungal pathogen that sheds polysaccharide (exo-ps) into host tissues. while shed exo-ps mediates numerous untoward effects (including promoting increased intracranial pressure), little is known about the regulation of this phenomenon. since downregulation of the allergen 1 (all1) gene is associated with high icp, we investigated the relationship between all1 expression and exo-ps structure using a variety of biophysical techniques. the δall1 mutants ...201323565821
biofilm from a clinical strain of cryptococcus neoformans activates the nlrp3 inflammasome. 201323567555
design, synthesis and antimicrobial activity of novel benzothiazole analogs.in an attempt to design and synthesize a new class of antimicrobials, dialkyne substituted 2-aminobenzothiazole was reacted with various substituted aryl azides to generate a small library of 20 compounds (3a-t) by click chemistry. structures of the newly synthesized compounds were established on the basis of spectral data. these compounds were screened for their antibacterial activity against gram+ bacteria (staphylococcus aureus and enterococcus faecalis), gram- bacteria (salmonella typhi, esc ...201323567952
antimicrobial potential of selected brown seaweeds from vedalai coastal waters, gulf of mannar.to evaluate the antimicrobial activity of turbinaria conoides (t. conoides), padina gymnospora (p. gymnospora) and sargassum tenerrimum against human bacterial and fungal pathogens.201123569739
pulmonary coinfection by pneumocystis jiroveci and cryptococcus neoformans.we communicate the diagnosis by microscopy of a pulmonary coinfection produced by cryptococcus neoformans and pneumocystis jiroveci, from a respiratory secretion obtained by bronchoalveolar lavage of an aids patient. our review of literature identified this coinfection as unusual presentation. opportunistic infections associated with hiv infection are increasingly recognized. it may occur at an early stage of hiv-infection. whereas concurrent opportunistic infections may occur, coexisting pneumo ...201223569840
in vitro antimicrobial activity of mangrove plant sonneratia alba.to investigate the antimicrobial property of mangrove plant sonneratia alba (s. alba).201223569943
pharmacokinetics and pharmacodynamics of fluconazole for cryptococcal meningoencephalitis: implications for antifungal therapy and in vitro susceptibility breakpoints.fluconazole is frequently the only antifungal agent that is available for induction therapy for cryptococcal meningitis. there is relatively little understanding of the pharmacokinetics and pharmacodynamics (pk-pd) of fluconazole in this setting. pk-pd relationships were estimated with 4 clinical isolates of cryptococcus neoformans. mics were determined using clinical and laboratory standards institute (clsi) methodology. a nonimmunosuppressed murine model of cryptococcal meningitis was used. mi ...201323571544
antifungal effect of lavender honey against candida albicans , candida krusei and cryptococcus neoformans.monofloral lavender honey samples (n = 30), were analyzed to test antifungal effect against candida albicans, candida krusei, and cryptococcus neoformans. the specific growth rates (μ) showed that all the yeast growths were reduced in the presence of honey. the honey concentration (% w/v) that inhibited 10% of the yeasts growth (x min) ranged from 31.0% (c. albicans), 16.8% (c. krusei) and 23.0% (c. neoformans). a synthetic honey solution was also tested to determine antifungal activity attribut ...201123572800
the impact of proteomics on the understanding of functions and biogenesis of fungal extracellular vesicles.several microbial molecules are released to the extracellular space in vesicle-like structures. in pathogenic fungi, these molecules include pigments, polysaccharides, lipids, and proteins, which traverse the cell wall in vesicles that accumulate in the extracellular space. the diverse composition of fungal extracellular vesicles (ev) is indicative of multiple mechanisms of cellular biogenesis, a hypothesis that was supported by ev proteomic studies in a set of saccharomyces cerevisiae strains w ...201423583696
regulation of copper toxicity by candida albicans gpa2.copper is an essential nutrient that is toxic to cells when present in excess. the fungal pathogen candida albicans employs several mechanisms to survive in the presence of excess copper, but the molecular pathways that govern these responses are not completely understood. we report that deletion of gpa2, which specifies a g-protein α subunit, confers increased resistance to excess copper and propose that the increased resistance is due to a combination of decreased copper uptake and an increase ...201323584994
titan cells in cryptococcus neoformans: cells with a giant impact.cryptococcus neoformans is a pathogenic yeast that commonly infects immunocompromised individuals, yet has developed multiple adaptation mechanisms to the host. several virulence factors (capsule and melanin) have been known for many years. however, this yeast also possesses a morphogenetic program that is still not well characterized. c. neoformans has the ability to dramatically enlarge its size during infection to form 'titan cells' that can reach up to 100μm in cell body diameter, in contras ...201323588027
brain inositol is a novel stimulator for promoting cryptococcus penetration of the blood-brain barrier.cryptococcus neoformans is the most common cause of fungal meningitis, with high mortality and morbidity. the reason for the frequent occurrence of cryptococcus infection in the central nervous system (cns) is poorly understood. the facts that human and animal brains contain abundant inositol and that cryptococcus has a sophisticated system for the acquisition of inositol from the environment suggests that host inositol utilization may contribute to the development of cryptococcal meningitis. in ...201323592982
hydroxyaldimines as potent in vitro anticryptococcal agents.cryptococcosis, a fungal infection that affects both immunocompromised and immunocompetent individuals, contributes to increasing indices of mortality and morbidity. the development of resistance by cryptococcus spp., the limited number of commercial antifungal drugs and the various side effects of these drugs cause the treatment of cryptococcosis to be a challenge. the in vitro anticryptococcal activity of nine hydroxyaldimines was evaluated against 24 strains of cryptococcus spp. antifungal su ...201323594040
[frequency distribution and antibiotic resistance of pathogens from the cerebrospinal fluid of 116 children with bacterial meningitis].to determine the frequency distribution and antibiotic resistance of pathogens isolated from the cerebrospinal fluid samples of children with bacterial meningitis (bm) and to provide a basis for the timely and effective treatment of childhood bm.201323607947
binding of the wheat germ lectin to cryptococcus neoformans chitooligomers affects multiple mechanisms required for fungal pathogenesis.the principal capsular component of cryptococcus neoformans, glucuronoxylomannan (gxm), interacts with surface glycans, including chitin-like oligomers. although the role of gxm in cryptococcal infection has been well explored, there is no information on how chitooligomers affect fungal pathogenesis. in this study, surface chitooligomers of c. neoformans were blocked through the use of the wheat germ lectin (wga) and the effects on animal pathogenesis, interaction with host cells, fungal growth ...201323608320
msi1-like (msil) proteins in fungi.msi1-like (msil) proteins, which are eukaryote-specific and contain a series of wd40 repeats, have pleiotropic roles in chromatin assembly, dna damage repair, and regulation of nutrient/stress-sensing signaling pathways. in the fungal kingdom, the functions of msil proteins have been studied most intensively in the budding yeast model saccharomyces cerevisiae, an ascomycete. yet their functions are largely unknown in other fungi. recently, an msil protein, msl1, was discovered and functionally c ...201323610533
prezygotic and postzygotic control of uniparental mitochondrial dna inheritance in cryptococcus neoformans.uniparental inheritance of mitochondrial dna is pervasive in nonisogamic higher eukaryotes during sexual reproduction, and postzygotic and/or prezygotic factors are shown to be important in ensuring such an inheritance pattern. although the fungus cryptococcus neoformans undergoes sexual production with isogamic partners of opposite mating types a and α, most progeny derived from such mating events inherit the mitochondrial dna (mtdna) from the a parent. the homeodomain protein complex sxi1α/sxi ...201323611907
microbiological, epidemiological, and clinical characteristics and outcomes of patients with cryptococcosis in taiwan, 1997-2010.among members of cryptococcus neoformans- cryptococcus gattii species complex, c. neoformans is distributed worldwide whereas c. gattii is considered to be more prevalent in the subtropics and tropics including taiwan. this nationwide study was undertaken to determine the distribution of genotypes, clinical characteristics and outcomes of 219 patients with proven cryptococcosis at 20 hospitals representative of all geographic areas in taiwan during 1997-2010.201323613973
facile construction of structurally diverse thiazolidinedione-derived compounds via divergent stereoselective cascade organocatalysis and their biological exploratory studies.in this article, we present a new approach by merging two powerful synthetic tactics, divergent synthesis and cascade organocatalysis, to create a divergent cascade organocatalysis strategy for the facile construction of new "privileged" substructure-based dos (pdos) library. as demonstrated, notably 5 distinct molecular architectures are produced facilely from readily available simple synthons thiazolidinedione and its analogues and α,β-unsaturated aldehydes in 1-3 steps with the powerful strat ...201323614347
cytotoxic and antibacterial substances against multi-drug resistant pathogens from marine sponge symbiont: citrinin, a secondary metabolite of penicillium sp.to isolate, purify, characterize, and evaluate the bioactive compounds from the sponge-derived fungus penicillium sp. ff001 and to elucidate its structure.201323620853
cryptococcal sternal osteomyelitis in a healthy woman: a review of cryptococcus neoformans.cryptococcus, an opportunistic yeast, known to afflict immune-compromised patients is often overlooked in immune-competent patients. this has led to increasing morbidity and mortality worldwide. we present a case of cryptococcus causing sternal osteomyelitis in an immune-competent individual. till date no case of cryptococcus causing sternal osteomyelitis in an immune-competent patient has been reported in the english literature since 1946-2011. with the rising incidence of cryptococcus infectio ...201323625673
cryptococcus neoformans constitutes an ideal model organism to unravel the contribution of cellular aging to the virulence of chronic infections.aging affects all organisms, from unicellular yeasts to multicellular humans. studies in model organisms demonstrate that the pathways that mediate the two forms of aging, replicative and chronological, are highly conserved. most studies are focused on the effect of aging on an individual cell rather than a whole population. complex longevity regulation, however, makes aging a highly adaptive trait that is subject to natural selection. recent studies have shed light on the potential relevance of ...201323631868
fungal virulence in a lepidopteran model is an emergent property with deterministic features.abstract virulence has been proposed to be an emergent property, which by definition implies that it is not reducible to its components, but this application of a philosophical concept to the host-microbe interaction has not been experimentally tested. the goals of our study were to analyze the correlation of the phenotype with the ability to cause disease and to determine the dynamics of an experimental cryptococcal infection in galleria mellonella and acanthamoeba castellanii. by studying the ...201323631914
breakthrough disseminated cryptococcosis during micafungin therapy.echinocandins are not active against basidiomycetous yeasts, such as cryptococcus neoformans, trichosporon, and rhodotorula species, and zygomycosis. we present a patient with renal failure and candidemia, who developed a breakthrough fungal infection with cryptococcemia and cryptococcuria while receiving micafungin therapy.201523632603
the crz1/sp1-like gene links survival under limited aeration, cell integrity and biofilm formation in the pathogenic yeast cryptococcus neoformans.limited aeration has been demonstrated to cause slowdown in proliferation and delayed budding, resulting eventually in a unique unbudded g2-arrest in the obligate aerobic pathogenic yeast cryptococcus neoformans. also, the ability to adapt to decreased oxygen levels during pathogenesis has been identified as a virulence factor in c. neoformans. the aim of this study was to identify and characterize genes that are necessary for the proliferation slowdown and g2-arrest caused by limited aeration.201423640031
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