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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
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
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
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
biofilm from a clinical strain of cryptococcus neoformans activates the nlrp3 inflammasome. 201323567555
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
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
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
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
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
donor transmission of cryptococcus neoformans presenting late after renal transplantation. 201326019853
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
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
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
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
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
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
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
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
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
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
advancing translational immunology in hiv-associated cryptococcal meningitis. 201323493727
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
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
[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
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
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
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
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
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
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
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
[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
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
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
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
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
[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
gastroduodenal cryptococcus in an aids patient presenting with melena.gastrointestinal cryptococcosis is extremely rare with only a few case reports found in the literature and involvement primarily identified post-mortem. this is a case of 54-year-old man with a 20-year history of poorly controlled human immunodeficiency virus presented with constitutional symptoms along with melena. diagnostic work up with esophagogastroduodenoscopy showed 4 irregular ulcers in the stomach notable for red-pigmented lesions within the ulcers, erythematous mucosa in the antrum and ...201327785222
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
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
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
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
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
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
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
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
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
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
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
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
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
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
cutaneous cryptococcoma in a patient on tnf-α inhibition.an 87-year old caucasian male with past medical history of rheumatoid arthritis (ra) and chronic kidney disease presents with left hand erythema, pain, tenderness, induration and edema. clinically, these hand findings began proximal to the metacarpo-phalangeal joints and extended to the distal wrist. he was noted to have ipsilateral axillary lymph node enlargement but denied any constitutional signs or symptoms. laboratory markers of inflammation were poor prognostic indicators due to relatively ...201326237147
opsonizing properties of rat ficolin-a in the defence against cryptococcus neoformans.cryptococcus neoformans is a pathogenic fungus causing life threatening infections in humans. the present in vitro study aimed to investigate the opsonizing properties of a well characterized serum ficolin (rat ficolin-a), a member of carbohydrate-recognition molecules of the innate immune system, in the defence against this fungal pathogen. using flow cytometric analysis we have been able to demonstrate that ficolin-a readily binds to two different acapsular c. neoformans serotypes (representat ...201322789560
genotyping and antifungal susceptibility testing of cryptococcus neoformans isolates from cameroonian hiv-positive adult patients.cryptococcus neoformans is the most common cause of meningitis amongst adult africans with hiv/aids. the widespread use of fluconazole may lead to the emergence of isolates with reduced susceptibility. we studied c. neoformans isolates from hiv-infected patients with cryptococcal meningitis. genotyping and antifungal testing were performed to assess the genetic diversity, occurrence of mixed infections and in vitro activity of antifungal agents. isolates were recovered from cerebrospinal fluid p ...201323033854
multilocus sequence typing of cryptococcus neoformans in non-hiv associated cryptococcosis in nagasaki, japan.cryptococcosis is primarily caused by two cryptococcus species, i.e., cryptococcus neoformans and c. gattii. both include several genetically diverse subgroups that can be differentiated using various molecular strain typing methods. since little is known about the molecular epidemiology of the c. neoformans/c. gattii species complex in japan, we conducted a molecular epidemiological analysis of 35 c. neoformans isolates from non-hiv patients in nagasaki, japan and 10 environmental isolates from ...201322901045
mixed pneumocystis and cryptococcus cutaneous infection histologically mimicking xanthoma.cutaneous pneumocystis jirovecii infection is rare. it is thought that the disease emerges from a latent infection delivered via hematogenous and/or lymphatic dissemination from a primary lung infection in immunocompromised individuals. a 32-year-old human immunodeficiency virus-positive male was admitted for headache and vomiting. he was diagnosed with meningitis due to cryptococcus neoformans and sputum tested positive for pneumocystis. six months later, he presented with a slightly crusted ye ...201322892474
large-scale evaluation of the immuno-mycologics lateral flow and enzyme-linked immunoassays for detection of cryptococcal antigen in serum and cerebrospinal fluid.cryptococcosis is a systemic infection caused by the pathogenic yeasts cryptococcus neoformans and c. gattii. detection of cryptococcal capsular antigen (crag) in serum and cerebrospinal fluid (csf) plays an important diagnostic role. we prospectively compared the new immuno-mycologics inc. (immy) lateral flow assay (lfa) and enzyme immunoassay (eia) to our current crag test (premier eia; meridian bioscience inc.). discordant samples were retested with the latex-cryptococcus antigen test (immy) ...201323114703
t1/st2 promotes t helper 2 cell activation and polyfunctionality in bronchopulmonary mycosis.interleukin (il)-33 enhances t helper (th)2 immunity via its receptor t1/st2. infection with the yeast-like pathogen cryptococcus neoformans is usually controlled by a th1-mediated immune response. the mechanisms responsible for nonprotective th2 immunity leading to allergic inflammation in pulmonary cryptococcosis are still not fully understood. using a murine pulmonary model of c. neoformans infection, we report that t1/st2 expression correlates with the intensity of th2 activation, as demonst ...201322990621
otitis interna induced by cryptococcus neoformans var. grubii in a cat.cryptococcus neoformans var. grubii was identified at necropsy in a case of bilateral otitis interna in a 7-year-old, female, domestic shorthair cat with a 9-day history of acute onset of vestibular disease. gross examination, including that of the middle and inner ears, was unremarkable. histologically, the auricular vestibuli, cochleae, and semicircular canals were bilaterally affected by granulomatous inflammation with extracellular and intrahistiocytic yeasts. the yeasts and associated infla ...201322700851
detection of cryptococcus neoformans capsular antigen in hiv-infected patients in the state of para in the north of brazil.cryptococcus neoformans is an important cause of morbidity in hiv-infected patients worldwide. in the northern region of brazil, the prevalence of this infection is poorly known due to a lack of systematic investigations. this study aimed to determine the occurrence of cryptococcosis by detecting antigenaemia in hiv-infected patients in the state of para, brazil. a latex cryptococcus antigen detection kit was used to test 418 serum samples from hiv-infected patients seen at two infectious diseas ...201324611754
matricellular protein cfl1 regulates cell differentiation.like higher eukaryotic cells in tissues, microbial cells in a community act in concert in response to environmental stimuli. they coordinate gene expression and their physiological and morphological states through intercellular communication mediated by matricellular signals. the adhesion protein cfl1 was recently shown to be a matricellular signal in regulating morphogenesis and biofilm formation in the eukaryotic microbe cryptococcus neoformans. cfl1 is naturally highly expressed in the hyphal ...201324567775
essential oil characterization of two azorean cryptomeria japonica populations and their biological evaluations.essential oils from foliage, bark and heartwood of cryptomeriajaponica d. don from azores archipelago (portugal) were analyzed by gc and gc-ms. two populations, of black and reddish heartwood color, were studied. the main compounds found in the foliage of both populations were alpha-pinene (9.6-29.5%), (+)-phyllocladene (3.5-26.5%), ent-kaur-16-ene (0.2-20.6%), sabinene (0.5-19.9%) and limonene (1.4-11.5%), with a large variation in individual compounds from each population. heartwood oils were ...201324555299
[cryptococcosis in hematology practice].to study the clinical manifestations of cryptococcosis, its diagnostic features, and treatment results in patients with hemoblastoses.201324432598
isolation of major components from the roots of godmania aesculifolia and determination of their antifungal activities.from the methanol root extract of godmania aesculifolia, a species selected in a multinational oas program aimed at discovering antifungal compounds from latin american plants, a new chavicol diglycoside (1), the known 3,4-dihydroxy-2-(3-methylbut-2-en-1-yl)-3,4-dihydronaphthalen-1(2h)-one (2), and lapachol (3) were isolated and characterized by 1d and 2d nmr and ms techniques. only 3 exhibited fairly good activity against a panel of clinical isolates of cryptococcus neoformans (mic50 between 7. ...201324356871
balancing stability and flexibility within the genome of the pathogen cryptococcus neoformans. 201324348244
meningitis due to cryptococcus gattii in an immunocompetent patient.the incidence of cryptococcal infection is high in developing countries such as india. cryptococcus gattii, formerly known as cryptococcus neoformans var gattii, is an encapsulated yeast that causes disease in both immunocompetent and immunosupressed individuals. the organism enters via respiratory tract and causes a spectrum of illness ranging from asymptomatic infection to severe illness, including pneumonia and disseminated infection involving multiple sites, including the central nervous sys ...201324298497
global molecular epidemiology of cryptococcus neoformans and cryptococcus gattii: an atlas of the molecular types.cryptococcosis is a fungal disease affecting more than one million people per year worldwide. the main etiological agents of cryptococcosis are the two sibling species cryptococcus neoformans and cryptococcus gattii that present numerous differences in geographical distribution, ecological niches, epidemiology, pathobiology, clinical presentation and molecular characters. genotyping of the two cryptococcus species at subspecies level supplies relevant information to understand how this fungus ha ...201324278784
cryptococcus gattii infections: contemporary aspects of epidemiology, clinical manifestations and management of infection.cryptococcus gattii is an important primary and opportunistic pathogen, predominantly causing meningoencephalitis and pulmonary disease with substantial mortality. initially considered geographically restricted to immune-competent, highly exposed individuals in the tropics, an apparent epidemic in north america has led to new perspectives on its ecology, epidemiology and clinical associations, which are distinct from its sibling species cryptococcus neoformans. the role of c. gattii molecular ge ...201324266360
the seasonal variation of the chemical composition of essential oils from porcelia macrocarpa r.e. fries (annonaceae) and their antimicrobial activity.this study investigates the impact of seasonal variation on the chemical composition of essential oils from the leaves of porcelia macrocarpa (annonaceae) obtained over the course of one year (january-december 2011) and the chemical composition of the essential oils obtained from the ripe fruits of the same plant. furthermore, the essential oils of the leaves were investigated with respect to their antimicrobial activity. the essential oils of the leaves contain a mixture of monoterpenes, one di ...201324189296
rnai function, diversity, and loss in the fungal kingdom.rnai is conserved and has been studied in a broad cross-section of the fungal kingdom, including neurospora crassa, schizosaccharomyces pombe, cryptococcus neoformans, and mucor circinelloides. and yet well known species, including the model yeast saccharomyces cerevisiae and the plant pathogen ustilago maydis, have lost rnai, providing insights and opportunities to illuminate benefits conferred both by the presence of rnai and its loss. some of the earliest studies of rnai were conducted in neu ...201324173579
identification and characterization of cryptococcus neoformans protein fractions that induce protective immune responses.cryptococcus neoformans, the main causative agent of cryptococcosis, is a fungal pathogen that causes life-threatening meningoencephalitis in immunocompromised patients. to date, there is no vaccine or immunotherapy approved to treat cryptococcosis. cell- and antibody-mediated immune responses collaborate to mediate optimal protection against c. neoformans infections. accordingly, we identified cryptococcal protein fractions capable of stimulating cell- and antibody-mediated immune responses and ...201324170628
cryptococcosis: epidemiology, fungal resistance, and new alternatives for treatment.cryptococcosis is an important systemic mycosis and the third most prevalent disease in human immunodeficiency virus (hiv)-positive individuals. the incidence of cryptococcosis is high among the 25 million people with hiv/acquired immunodeficiency syndrome (aids), with recent estimates indicating that there are one million cases of cryptococcal meningitis globally per year in aids patients. in cryptococcus neoformans, resistance to azoles may be associated with alterations in the target enzyme e ...201324141976
relevance of intracranial hypertension control in the management of cryptococcus neoformans meningitis related to aids.to evaluate the relationship between intracranial hyperpressure (hicp) and mortality in patients with cryptococcal meningitis related to aids (cmra).201324122543
central nervous system and cryptococcus neoformans. 201324083226
biologically active secondary metabolites from asphodelus microcarpus.bioassay guided fractionation of the ethanolic extract of asphodelus microcarpus salzm.et vivi (asphodelaceae) resulted in the isolation of one new metabolite, 1,6-dimethoxy-3-methyl-2-naphthoic acid (1) as well as nine known compounds: asphodelin (2), chrysophanol (3), 8-methoxychrysophanol (4), emodin (5), 2-acetyl-1,8-dimethoxy-3-methylnaphthalene (6), 10-(chrysophanol-7'-yl)-10-hydroxychrysophanol-9-anthrone (7), aloesaponol-iii-8-methyl ether (8), ramosin (9) and aestivin (10). the compound ...201324079182
stress signaling pathways for the pathogenicity of cryptococcus.sensing, responding, and adapting to the surrounding environment are crucial for all living organisms to survive, proliferate, and differentiate in their biological niches. this ability is also essential for cryptococcus neoformans and its sibling species cryptococcus gattii, as these pathogens have saprobic and parasitic life cycles in natural and animal host environments. the ability of cryptococcus to cause fatal meningoencephalitis is highly related to its capability to remodel and optimize ...201324078305
multifocal cryptococcus neoformans var. neoforms: infection, treatment, and monitoring by serial computed tomography in a schmidt's red-tailed guenon (cercopithecus ascanius schmidti).a 9-yr-old, female, intact schmidt's red-tailed guenon (cercopithecus ascanius schmidti) presented with an acute swelling, consistent with an abscess over the right hip. cytology, culture, and polymerase chain reaction (pcr) results from material within the abscess and serum titers were all indicative of a cryptococcus neoformans infection. thoracic radiographs and computed tomography (ct) revealed a consolidated right caudal lung lobe associated with an endobronchial mass. pulmonary cryptococcu ...201324063102
unisexual and heterosexual meiotic reproduction generate aneuploidy and phenotypic diversity de novo in the yeast cryptococcus neoformans.aneuploidy is known to be deleterious and underlies several common human diseases, including cancer and genetic disorders such as trisomy 21 in down's syndrome. in contrast, aneuploidy can also be advantageous and in fungi confers antifungal drug resistance and enables rapid adaptive evolution. we report here that sexual reproduction generates phenotypic and genotypic diversity in the human pathogenic yeast cryptococcus neoformans, which is globally distributed and commonly infects individuals w ...201324058295
how histopathology can contribute to an understanding of defense mechanisms against cryptococci.invasive fungal infections, particularly those considered opportunistic, have become a common and significant complication of procedures performed in advanced contemporary medicine. among such infections, cryptococcosis, which is usually caused by infection with cryptococcus neoformans and cryptococcus gattii, is particularly problematic because this fungal infection occurs in immunocompromised and apparently immunocompetent individuals. it has been largely accepted that cryptococcus species are ...201324058271
new insights into hiv/aids-associated cryptococcosis.cryptococcal meningitis is a life-threatening opportunistic fungal infection in both hiv-infected and hiv-uninfected patients. according to the most recent taxonomy, the responsible fungus is classified into a complex that contains two species (cryptococcus neoformans and c. gattii), with eight major molecular types. hiv infection is recognized worldwide as the main underlying disease responsible for the development of cryptococcal meningitis (accounting for 80-90% of cases). in several areas of ...201324052889
chiral n-benzyl-n-methyl-1-(naphthalen-1-yl)ethanamines and their in vitro antifungal activity against cryptococcus neoformans, trichophyton mentagrophytes and trichophyton rubrum.in the search for new antifungal compounds and to explore structure activity relationships, a series of 24 chiral benzyl amine type antifungals was synthesised and characterised. in vitro testing against the human pathogen cryptococcus neoformans revealed that several derivatives had mic50 values similar to that of the commercial drug butenafine. all of these contained a bulky group in the para position of the benzyl fragment. eighteen compounds were also tested for activity against the dermatop ...201324051242
cryptococcal meningitis with secondary cutaneous involvement in an immunocompetent host.cryptococcosis is a potentially fatal fungal disease caused by variants of cryptococcus neoformans species.  the respiratory tract is the usual portal of entry, with a peculiar predilection to invade the central nervous system.  the skin can be secondarily involved in disseminated infection or be exceptionally involved as primary cutaneous infection by inoculation.  the disease is mostly seen in immunodeficiency states.  the diagnosis is frequently unsuspected in immunocompetent patients. we rep ...201324042105
elucidating the immunological function of the cryptococcus neoformans capsule.the encapsulated fungal pathogen cryptococcus neoformans represents a significant agent of life-threatening infections in immunocompromised subjects. a unique characteristic of cryptococcus species is the presence of a polysaccharide capsule, which is essential for virulence and endows cryptococcus with potent immunoregulatory properties. this review provides an overview of the immunological properties of the principal components of c. neoformans capsule.201324020739
geographically structured populations of cryptococcus neoformans variety grubii in asia correlate with hiv status and show a clonal population structure.cryptococcosis is an important fungal disease in asia with an estimated 140,000 new infections annually the majority of which occurs in patients suffering from hiv/aids. cryptococcus neoformans variety grubii (serotype a) is the major causative agent of this disease. in the present study, multilocus sequence typing (mlst) using the isham mlst consensus scheme for the c. neoformans/c. gattii species complex was used to analyse nucleotide polymorphisms among 476 isolates of this pathogen obtained ...201324019866
a case of disseminated cryptococcosis with skin manifestations in a patient with newly diagnosed hiv.in this case report, we provide a concise review of the pathogenesis, clinical presentation, key diagnostic findings, and treatment options for cryptococcus. cryptococcus neoformans is a ubiquitous dimorphic fungus that can potentially be life threatening, especially in immunocompromised hosts. it commonly infects the respiratory tract or central nervous system. however, skin manifestations can be a marker of severe and disseminated disease, particularly in individuals at higher risk, including ...201324015436
restricted substrate specificity for the geranylgeranyltransferase-i enzyme in cryptococcus neoformans: implications for virulence.proper cellular localization is required for the function of many proteins. the caax prenyltransferases (where caax indicates a cysteine followed by two aliphatic amino acids and a variable amino acid) direct the subcellular localization of a large group of proteins by catalyzing the attachment of hydrophobic isoprenoid moieties onto c-terminal caax motifs, thus facilitating membrane association. this group of enzymes includes farnesyltransferase (ftase) and geranylgeranyltransferase-i (ggtase-1 ...201324014765
antifungal, antioxidant and anti-inflammatory activities of oenanthe crocata l. essential oil.the present study reports the chemical composition, antifungal, antioxidant and anti-inflammatory properties as well as the cytotoxicity of oenanthe crocata essential oil and one of its main compounds. the essential oil was obtained from the aerial parts of the plant by hydrodistillation and analysed by gc and gc/ms. the oil was predominantly composed of monoterpene hydrocarbons (85.8%), being the main compounds trans-β-ocimene (31.3%), sabinene (29.0%) and cis-β-ocimene (12.3%). for the antifun ...201324012643
sulphiredoxin plays peroxiredoxin-dependent and -independent roles via the hog signalling pathway in cryptococcus neoformans and contributes to fungal virulence.mechanisms of oxidative stress resistance are crucial virulence factors for survival and proliferation of fungal pathogens within the human host. in this study we have identified and functionally characterized the role of sulphiredoxin, srx1, in oxidative stress resistance of cryptococcus neoformans causing fungal meningoencephalitis and regulation of peroxiredoxins, tsa1 and tsa3, and thioredoxins, trx1 and trx2. the c. neoformans hog (high osmolarity glycerol response) pathway was essential fo ...201323998805
azole resistance in cryptococcus gattii from the pacific northwest: investigation of the role of erg11.cryptococcus gattii is responsible for an expanding epidemic of serious infections in western canada and the northwestern united states (pacific northwest). some patients with these infections respond poorly to azole antifungals, and high azole mics have been reported in pacific northwest c. gattii. in this study, multiple azoles (but not amphotericin b) had higher mics for 25 pacific northwest c. gattii than for 34 non-pacific northwest c. gattii or 20 cryptococcus neoformans strains. we theref ...201323979758
nitrogen source-dependent capsule induction in human-pathogenic cryptococcus species.cryptococcus neoformans and c. gattii cause meningoencephalitis and are an increasing human health threat. these pathogenic cryptococcus species are neurotropic and persist in the cerebrospinal fluid (csf) of the mammalian host during infection. in order to survive in the host, pathogenic fungi must procure nutrients, such as carbon and nitrogen, from the csf. to enhance our understanding of nutrient acquisition during central nervous system infection by cryptococcus species, we examined the uti ...201323975889
introns regulate gene expression in cryptococcus neoformans in a pab2p dependent pathway.most cryptococccus neoformans genes are interrupted by introns, and alternative splicing occurs very often. in this study, we examined the influence of introns on c. neoformans gene expression. for most tested genes, elimination of introns greatly reduces mrna accumulation. strikingly, the number and the position of introns modulate the gene expression level in a cumulative manner. a screen for mutant strains able to express functionally an intronless allele revealed that the nuclear poly(a) bin ...201323966870
temporal behavior of capsule enlargement by cryptococcus neoformans.microbial capsules are important virulence traits that mediate cell-host interactions and provide protection against host immune defense mechanisms. cryptococcus neoformans is a yeast-like fungus that is capable of synthesizing a complex polysaccharide (ps) capsule that is required for causing disease. microscopic visualization of capsule enlargement is difficult, because the capsule is a highly hydrated structure with an index of refraction that is very close to that of aqueous medium. in this ...201323954840
the heat shock protein (hsp) 70 of cryptococcus neoformans is associated with the fungal cell surface and influences the interaction between yeast and host cells.the pathogenic yeast cryptococcus neoformans secretes numerous proteins, such as heat shock proteins, by unconventional mechanisms during its interaction with host cells. hsp70 is a conserved chaperone that plays important roles in various cellular processes, including the interaction of fungi with host immune cells. here, we report that sera from individuals with cryptococcosis infection recognize a recombinant c. neoformans hsp70 (cn_rhsp70). moreover, immunofluorescence assays using antibodie ...201323954835
ras1 acts through duplicated cdc42 and rac proteins to regulate morphogenesis and pathogenesis in the human fungal pathogen cryptococcus neoformans.proliferation and morphogenesis in eukaryotic cells depend on the concerted activity of rho-type gtpases, including ras, cdc42, and rac. the sexually dimorphic fungus cryptococcus neoformans, which encodes paralogous, non-essential copies of all three, provides a unique model in which to examine the interactions of these conserved proteins. previously, we demonstrated that ras1 mediates c. neoformans virulence by acting as a central regulator of both thermotolerance and mating. we report here th ...201323950731
prevalence and antifungal susceptibility of cryptococcus neoformans isolated from pigeon excreta in chon buri province, eastern thailand.the prevalence of cerebral meningitis caused by cryptococcus neoformans in hiv-infected patients in eastern thailand is high. however, little is known about the occurrence of this pathogenic yeast in the environment of this region.  the aim of our study was to characterize the prevalence of c. neoformans, its serotypes and antifungal drug susceptibilities in environmental isolates from chon buri, eastern thailand.  c. neoformans was isolated from 10% of fifty pigeon excreta examined from this pr ...201323995421
fc gamma receptor 3a polymorphism and risk for hiv-associated cryptococcal disease.cryptococcus neoformans is one of the most common causes of fungal disease in hiv-infected persons, but not all of those who are infected develop cryptococcal disease (cd). although cd4(+) t cell deficiency is a risk factor for hiv-associated cd, polymorphisms of phagocytic fc gamma receptors (fcgrs) have been linked to cd risk in hiv-uninfected persons. to investigate associations between fcgr2a 131 h/r and fcgr3a 158 f/v polymorphisms and cd risk in hiv-infected persons, we performed pcr-based ...201323982074
old cryptococcus neoformans cells contribute to virulence in chronic cryptococcosis.does cell age matter in virulence? the emergence of persister cells during chronic infections is critical for persistence of infection, but little is known how this occurs. here, we demonstrate for the first time that the replicative age of the fungal pathogen cryptococcus neoformans contributes to persistence during chronic meningoencephalitis. generationally older c. neoformans cells are more resistant to hydrogen peroxide stress, macrophage intracellular killing, and antifungal agents. older ...201323943761
the calcium transporter pmc1 provides ca2+ tolerance and influences the progression of murine cryptococcal infection.the ca(2+)-calcineurin signaling pathway in the human fungal pathogen cryptococcus neoformans is essential for adaptation to the host environment during infection. calcium transporters regulate cytosolic calcium concentrations, providing ca(2+) loading into storage organelles. the three calcium transporters that have been characterized in c. neoformans, cch1, eca1 and vcx1, are required for fungal virulence, supporting a role for calcium-mediated signaling in cryptococcal pathogenesis. in the pr ...201323895559
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