Publications

TitleAbstractYear
Filter
PMID(sorted ascending)
Filter
disseminated cryptococcal lymphadenitis with negative latex agglutination test.we reported an unusual case of disseminated cryptococcal lymphadenitis in an immunocompetent host who presented with fever and lymphadenopathy, which were the only two symptoms and signs. latex agglutination test of serum and cerebrospinal fluid (csf) were negative, while lymph node biopsy showed cryptococcus neoformans. a diagnosis of disseminated cryptococcal lymphadenitis was made. then the patient was treated with amphotericin b for 15 days as initial therapy and itraconazole for 6 months as ...201222882869
roles of cch1 and mid1 in morphogenesis, oxidative stress response and virulence in candida albicans.ca(2+) channel cch1, and its subunit mid1, has been suggested as the protein complex responsible for mediating ca(2+) influx, which is often employed by fungal cells to maintain cell survival. the abilities of morphological switch and response to stress conditions are closely related to pathogenicity in candida albicans. cch1 and mid1 activity are required for virulence of cryptococcus neoformans and claviceps purpurea, respectively. to investigate whether cch1 and mid1 also play a role in the v ...201222886468
titan cell production enhances the virulence of cryptococcus neoformans.infection with cryptococcus neoformans begins when desiccated yeast cells or spores are inhaled and lodge in the alveoli of the lungs. a subset of cryptococcal cells in the lungs differentiate into enlarged cells, referred to as titan cells. titan cells can be as large as 50 to 100 μm in diameter and exhibit a number of features that may affect interactions with host immune defenses. to characterize the effect of titan cell formation on the host-pathogen interaction, we utilized a previously des ...201222890995
synthesis and antifungal activity of derivatives of 2- and 3-benzofurancarboxylic acids.we found that amiodarone has potent antifungal activity against a broad range of fungi, potentially defining a new class of antimycotics. investigations into its molecular mechanisms showed amiodarone mobilized intracellular ca2+, which is thought to be an important antifungal characteristic of its fungicidal activity. amiodarone is a synthetic drug based on the benzofuran ring system, which is contained in numerous compounds that are both synthetic and isolated from natural sources with antifun ...201222892340
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
cryptococcus neoformans activates rhogtpase proteins followed by protein kinase c, focal adhesion kinase, and ezrin to promote traversal across the blood-brain barrier.cryptococcus neoformans is an opportunistic fungal pathogen that causes meningoencephalitis. previous studies have demonstrated that cryptococcus binding and invasion of human brain microvascular endothelial cells (hbmec) is a prerequisite for transmigration across the blood-brain barrier. however, the molecular mechanism involved in the cryptococcal blood-brain barrier traversal is poorly understood. in this study we examined the signaling events in hbmec during interaction with c. neoformans. ...201222898813
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
inhibition of α-class cytosolic human carbonic anhydrases i, ii, ix and xii, and β-class fungal enzymes by carboxylic acids and their derivatives: new isoform-i selective nanomolar inhibitors.the members of a focused series of carboxylic acids and of their derivatives (esters, amides and metal complexes) have been investigated as inhibitors of the main cytosolic/transmembrane carbonic anhydrase isoforms, ca i, ii, ix and xii, belonging to the mammalian α-class of cas. these enzymes are present in red blood cells in submillimolar concentration, and typical sulfonamide ca inhibitors do not selectively inhibit any of them. among such isozymes, the isoform-i is an 'orphan' target that me ...201222901388
main-chain imidazolium oligomer material as a selective biomimetic antimicrobial agent.human health has been challenged by multi-drug-resistant microorganisms for several decades. herein, we have developed a main-chain imidazolium oligomer (ibn-1) material to combat broad spectrum of pathogenic strains, including drug-resistant klebsiella pneumoniae, vancomycin-resistant enterococcus, methicillin-resistant staphylococcus aureus and fluconazole-resistant yeast cryptococcus neoformans, while displaying minimal hemolysis (hc(50)/mic values over 3000) and a very high therapeutic index ...201222902059
influence of iron regulation on the metabolome of cryptococcus neoformans.iron is an essential nutrient for virtually all organisms and acts as a cofactor for many key enzymes of major metabolic pathways. furthermore, iron plays a critical role in pathogen-host interactions. in this study, we analyzed metabolomic changes associated with iron availability and the iron regulatory protein cir1 in a human fungal pathogen cryptococcus neoformans. our metabolite analysis revealed that cir1 influences the glycolytic pathway, ergosterol biosynthesis and inositol metabolism, w ...201222911836
[intraventricular cryptococcoma successfully treated with liposomal amphotericin b and voriconazole: a case report].cryptococcal infections of the central nervous system (cns) are infrequent in immunocompetent hosts and usually present as meningitis. however, fungal masses called cryptococcoma can sometimes be formed. we report a case in which intraventricular cryptococcoma in an immunocompetent patient was completely cured using liposomal amphotericin b (l-amb) and voriconazole (vrcz). a 56-year-old previously healthy man was admitted to our hospital with fever, headache and bilateral hand tremor lasting ove ...201222915699
transgene induced co-suppression during vegetative growth in cryptococcus neoformans.introduction of dna sequences into the genome often results in homology-dependent gene silencing in organisms as diverse as plants, fungi, flies, nematodes, and mammals. we previously showed in cryptococcus neoformans that a repeat transgene array can induce gene silencing at a high frequency during mating (∼50%), but at a much lower frequency during vegetative growth (∼0.2%). here we report a robust asexual co-suppression phenomenon triggered by the introduction of a cpa1::ade2 transgene. multi ...201222916030
[cryptococcal meningitis as initial presentation of systemic lupus erythematosus].infection is one of the most frequent etiology of morbidity and mortality in patients with systemic lupus erythematosus (sle). cryptococcal meningitis is a recognized complication of sle with high mortality rates in those treated with immunosuppressive agents. we describe a patient with cryptoccoccal meningitis and sle. this case suggests that intrinsic immunological abnormality related to sle predisposed to opportunistic infections.201222917073
the antimicrobial, antioxidative, anti-inflammatory activity and cytotoxicity of different fractions of four south african bauhinia species used traditionally to treat diarrhoea.many bauhinia species, including those indigenous to south africa, are used in traditional medicine across the world for treating ailments such as gastrointestinal tract (git) disorders, diabetes, infectious diseases and inflammation.201222917809
central nervous system strongyloidiasis and cryptococcosis in an hiv-infected patient starting antiretroviral therapy.we report a case of strongyloides stercoralis hyperinfection syndrome with central nervous system involvement, in a patient with late human immunodeficiency virus (hiv) infection starting antiretroviral therapy, in whom strongyloides stercoralis larvae and cryptococcus neoformans were isolated antemortem from cerebrospinal fluid. our patient was not from an endemic region for the parasite, so strongyloidiasis was not originally suspected. for this reason, we conclude that strongyloides stercoral ...201222924046
effects of pimenta pseudocaryophyllus (gomes) l. r. landrum, on melanized and non-melanized cryptococcus neoformans.in the present study, the in vitro susceptibility and capsular width from both melanized and non-melanized cryptococcus neoformans cells in the presence of pimenta pseudocaryophyllus crude extract were determined. the results were compared with those obtained for voriconazole and amphotericin b. melanization was obtained in minimal medium broth with the addition of l-dopa, and the antifungal susceptibility tests were performed using the broth microdilution method. capsular width of 30 cells of e ...201222932958
edta inhibits biofilm formation, extracellular vesicular secretion, and shedding of the capsular polysaccharide glucuronoxylomannan by cryptococcus neoformans.the fungal pathogen cryptococcus neoformans can grow as a biofilm on a range of synthetic and prosthetic materials. cryptococcal biofilm formation can complicate the placement of shunts used to relieve increased intracranial pressure in cryptococcal meningitis and can serve as a nidus for chronic infection. biofilms are generally advantageous to pathogens in vivo, as they can confer resistance to antimicrobial compounds, including fluconazole and voriconazole in the case of c. neoformans. edta c ...201222941091
cryptococcus neoformans-cryptococcus gattii species complex: an international study of wild-type susceptibility endpoint distributions and epidemiological cutoff values for fluconazole, itraconazole, posaconazole, and voriconazole.epidemiological cutoff values (ecvs) for the cryptococcus neoformans-cryptococcus gattii species complex versus fluconazole, itraconazole, posaconazole, and voriconazole are not available. we established ecvs for these species and agents based on wild-type (wt) mic distributions. a total of 2,985 to 5,733 clsi mics for c. neoformans (including isolates of molecular type vni [mics for 759 to 1,137 isolates] and vnii, vniii, and vniv [mics for 24 to 57 isolates]) and 705 to 975 mics for c. gattii ...201222948877
t-2307 causes collapse of mitochondrial membrane potential in yeast.t-2307, an arylamidine compound, has been previously reported to have broad-spectrum in vitro and in vivo antifungal activities against clinically significant pathogens, including candida species, cryptococcus neoformans, and aspergillus species, and is now undergoing clinical trials. here we investigated the mechanism of action of t-2307 using yeast cells and mitochondria isolated from yeast and rat liver. nonfermentative growth of candida albicans and saccharomyces cerevisiae in glycerol mediu ...201222948882
disseminated cryptococcosis in an immunocompetent patient: a case report.cryptococcus neoformans is ubiquitous encapsulated yeast found throughout the world. it predominantly causes significant infections in immunocompromised individuals, of which 80-90% occur in people with human immunodeficiency virus (hiv) infection. disseminated cryptococcal infection is uncommon and almost always occurs in hiv-infected patients. disseminated disease, especially noncutaneous cryptococcal abscess in immunocompetent hosts, is exceedingly rare. we report a case of disseminated crypt ...201222953139
chemical and antifungal investigations of six lippia species (verbenaceae) from brazil.the lippia genus is used in ethnobotany as food, beverages, seasoning and antiseptic remedies, among others. the chemical compositions of fifteen extracts of six lippia species were investigated comparatively by hplc-pda. to avoid data replication of previous works on this genus, lippia lupulina cham. root ethanol extract was selected for isolation procedures based on principal component analyses (pca) of such data. seven compounds previously unreported in this genus were isolated from this extr ...201222953960
an antimicrobial evaluation of plants used for the treatment of respiratory infections in rural maputaland, kwazulu-natal, south africa.abundant availability of medicinal plants in the study area offers low cost health care, but scientific validation is needed in order to lend credibility to the traditional use against respiratory infections.201222960551
three bioactive sesquiterpene quinones from the fijian marine sponge of the genus hippospongia.a sesquiterpenoid quinone, epi-ilimaquinone (1), and two sesquiterpene amino quinones, smenospongine (2) and glycinylilimaquinone (3), were isolated from the fijian marine sponge hippospongia sp. the structures of these compounds were determined by spectroscopic analysis. compounds 1 and 3 were reported for the first time in this study from the sponge of the genus hippospongia. compound 1 displayed potent cytotoxic activity and showed antibacterial activity against methicillin-resistant staphylo ...201322963320
real-time in vivo imaging of fungal migration to the central nervous system.recent technical advances have afforded valuable new insights into the pathogenesis of fungal infections in the central nervous system (cns), which continue to cause devastating complications, particularly in immunocompromised individuals. to cause cns mycosis, organisms such as cryptococcus neoformans become blood borne and progress through a series of pathogenic checkpoints that culminate in fungal replication in the brain. critical steps include fungal arrest in the vasculature of the brain, ...201222966777
vaccine and immunotherapeutic approaches for the prevention of cryptococcosis: lessons learned from animal models.cryptococcus neoformans and c. gattii, the predominant etiological agents of cryptococcosis, can cause life-threatening infections of the central nervous system in immunocompromised and immunocompetent individuals. cryptococcal meningoencephalitis is the most common disseminated fungal infection in aids patients, and c. neoformans remains the third most common invasive fungal infection among organ transplant recipients. current anti-fungal drug therapies are oftentimes rendered ineffective due t ...201222973262
isolation of the volatile fraction from apium graveolens l. (apiaceae) by supercritical carbon dioxide extraction and hydrodistillation: chemical composition and antifungal activity.apium graveolens l. (wild celery), belonging to the family of apiaceae, is a scaposus hemicryptophyte. instead, the cultivate plant is an annual or biennial herb widely used as a spice and seasoning in food. a broad range of biological activities have been attributed to a. graveolens. these include antimicrobial activity, larvicidal activity, hepatoprotective activity, nematicidal and mosquito repellent potential and antihyperlipidaemic properties.in this study, the authors compare the compositi ...201322974401
a defect in iron uptake enhances the susceptibility of cryptococcus neoformans to azole antifungal drugs.the high-affinity reductive iron uptake system that includes a ferroxidase (cfo1) and an iron permease (cft1) is critical for the pathogenesis of cryptococcus neoformans. in addition, a mutant lacking cfo1 or cft1 not only has reduced iron uptake but also displays a markedly increased susceptibility to azole antifungal drugs. altered antifungal susceptibility of the mutants was of particular interest because the iron uptake system has been proposed as an alternative target for antifungal treatme ...201222975303
protective immunity against pulmonary cryptococcosis is associated with stat1-mediated classical macrophage activation.experimental pulmonary cryptococcus neoformans infection in balb/c mice is associated with polarized th2-type cytokine production, alternative macrophage activation, and severe bronchopneumonia. in contrast, pulmonary infection with a c. neoformans strain that secretes ifn-γ, h99γ, elicits th1-type cytokine production and classical macrophage activation. additionally, mice infected with h99γ resolve the acute infection and are subsequently protected against challenge with wild-type c. neoformans ...201222984078
susceptibility to progressive cryptococcus neoformans pulmonary infection is regulated by loci on mouse chromosomes 1 and 9.genetic factors that regulate the pathogenesis of pneumonia caused by the fungus cryptococcus neoformans are poorly understood. through a phenotypic strain survey we observed that inbred c3h/hen mice develop a significantly greater lung fungal burden than mice of the resistant cba/j strain 4 weeks following intratracheal infection with c. neoformans atcc 24067. the aim of the present study was to characterize the inflammatory response of c3h/hen mice following c. neoformans pulmonary infection a ...201222988020
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
structure-activity relationship study of nitrosopyrimidines acting as antifungal agents.the design, synthesis, in vitro evaluation, and conformational study of nitrosopyrimidine derivatives acting as antifungal agents are reported. different compounds structurally related with 4,6-bis(alkyl or arylamino)-5-nitrosopyrimidines were evaluated. some of these nitrosopyrimidines have displayed a significant antifungal activity against human pathogenic strains. in this paper, we report a new group of nitrosopyrimidines acting as antifungal agents. among them, compounds 2a, 2b and 15, the ...201222995772
pseudohyphal growth of cryptococcus neoformans is a reversible dimorphic transition in response to ammonium that requires amt1 and amt2 ammonium permeases.cryptococcus neoformans is a human-pathogenic basidiomycete that commonly infects hiv/aids patients to cause meningoencephalitis (7, 19). c. neoformans grows as a budding yeast during vegetative growth or as hyphae during sexual reproduction. pseudohyphal growth of c. neoformans has been observed rarely during murine and human infections but frequently during coculture with amoeba; however, the genetics underlying pseudohyphal growth are largely unknown. our studies found that c. neoformans disp ...201223002105
a paracoccidioides brasiliensis glycan shares serologic and functional properties with cryptococcal glucuronoxylomannan.the cell wall of the yeast form of the dimorphic fungus paracoccidioides brasiliensis is enriched with α1,3-glucans. in cryptococcus neoformans, α1,3-glucans interact with glucuronoxylomannan (gxm), a heteropolysaccharide that is essential for fungal virulence. in this study, we investigated the occurrence of p. brasiliensis glycans sharing properties with cryptococcal gxm. protein database searches in p. brasiliensis revealed the presence of sequences homologous to those coding for enzymes invo ...201223010152
cryptococcal genotype influences immunologic response and human clinical outcome after meningitis.in sub-saharan africa, cryptococcal meningitis (cm) continues to be a predominant cause of aids-related mortality. understanding virulence and improving clinical treatments remain important. to characterize the role of the fungal strain genotype in clinical disease, we analyzed 140 cryptococcus isolates from 111 ugandans with aids and cm. isolates consisted of 107 nonredundant cryptococcus neoformans var. grubii strains and 8 c. neoformans var. grubii/neoformans hybrid strains. multilocus sequen ...201223015735
unraveling the antifungal activity of a south american rattlesnake toxin crotamine.crotamine is a highly basic peptide from the venom of crotalus durissus terrificus rattlesnake. its common gene ancestry and structural similarity with the β-defensins, mainly due to an identical disulfide bond pattern, stimulated us to assess the antimicrobial properties of native, recombinant, and chemically synthesized crotamine. antimicrobial activities against standard strains and clinical isolates were analyzed by the colorimetric microdilution method showing a weak antibacterial activity ...201323022146
identification of genes from the fungal pathogen cryptococcus neoformans related to transmigration into the central nervous system.a mouse brain transmigration assessment (mbta) was created to investigate the central nervous system (cns) pathogenesis of cryptococcal meningoencephalitis.201223028773
primary cryptococcal prostatitis--rare occurrence.cryptococcosis is a well recognized infection in immunocompromised patients. cryptococcal infection primarily involves the lung and is hematogeneously spread to other organs. sometimes it might affect the genitourinary tract. the prostate gland is a rare site of primary infection due to cryptococcus neoformans. we report a case of granulomatous inflammation in the prostate as a result of crypyococcus neoformans infection in a 70 year old immunocompetent patient, a non diabetic, which was diagnos ...201223029729
role of ctr4 in the virulence of cryptococcus neoformans.while research has identified an important contribution for metals, such as iron, in microbial pathogenesis, the roles of other transition metals, such as copper, remain mostly unknown. recent evidence points to a requirement for copper homeostasis in the virulence of cryptococcus neoformans based on a role for a cuf1 copper regulatory factor in mouse models and in a human patient cohort. c. neoformans is an important fungal pathogen that results in an estimated 600,000 aids-related deaths yearl ...201223033470
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
in vitro susceptibilities of yeast species to fluconazole and voriconazole as determined by the 2010 national china hospital invasive fungal surveillance net (chif-net) study.we conducted active, laboratory-based surveillance for isolates from patients with invasive infections across china from august 2009 to july 2010. dna sequencing methods were used to define species, and susceptibility to fluconazole and voriconazole was determined by the clinical and laboratory standards institute m44-a2 disk diffusion method but using up-to-date clinical breakpoints or epidemiological cutoff values. candida spp. made up 90.5% of the 814 yeast strains isolated, followed by crypt ...201223035204
aetiological agents of cerebrospinal meningitis: a retrospective study from a teaching hospital in ghana.meningitis is an important cause of morbidity and mortality in low-resource settings. in sub-saharan africa, the meningitis belt has been characterized by particularly high and seasonal incidences of bacterial meningitis extending throughout life. despite the progress being made in treating the condition, the mortality rates continue to be high, ranging between 2% and 30% globally. in ghana, the mortality rate of meningitis has been estimated to range from 36% to 50%. however little information ...201223035960
synthesis and antifungal activity of diverse c-2 pyridinyl and pyridinylvinyl substituted quinolines.diverse 2-pyridinyl quinolines 6-12 and 2-pyridinilvinyl quinolines 13-17 were prepared using a straightforward synthesis based on the bicl(3)-catalyzed multicomponent imino diels-alder (imino da) reaction or a novel tandem imino da/catalytic tetrahydroquinoline ring oxidation/perkin condensation sequential process. all members of the series showed activities against dermatophytes and some of them possessed a broad spectrum of action. 2-(pyridin-4-yl)quinoline 9 and 2-(2-pyridin-4-yl)vinyl)quino ...201223036332
antitumor, antibiotic and antileishmanial properties of the pyranonaphthoquinone psychorubrin from mitracarpus frigidus.the bioactivity guided fractionation of the dichloromethane extract of mitracarpus frigidus afforded the pyranonaphthoquinone psychorubrin. this compound, hitherto unknown in the genus mitracarpus, had its biological activity evaluated against one panel of bacteria and two fungi, three tumor cell lines (hl60, jurkat and mcf-7) and four leishmania species. its identity was confirmed unambiguously by (1)h, (13)c, (1)h-cosy, ir and uv-vis spectroscopy and mass spectrometry. psychorubrin displayed a ...201223037306
[invasive mycoses during hematopoietic stem cell transplantation].to define the frequency, etiology, and risk factors of invasive mycoses (im) in patients with allogeneic (allo) and autologous (auto) hematopoietic stem cell transplantation (hsct) and to evaluate the impact of im on overall survival (os).201223038972
pleiotropic roles of the msi1-like protein msl1 in cryptococcus neoformans.msi1-like (msil) proteins contain wd40 motifs and have a pleiotropic cellular function as negative regulators of the ras/cyclic amp (camp) pathway and components of chromatin assembly factor 1 (caf-1), yet they have not been studied in fungal pathogens. here we identified and characterized an msil protein, msl1, in cryptococcus neoformans, which causes life-threatening meningoencephalitis in humans. notably, msl1 plays pleiotropic roles in c. neoformans in both camp-dependent and -independent ma ...201223042129
antifungal activity and composition of essential oils of conyza canadensis herbs and roots.essential oils from herbs and roots of conyza canadensis (horseweed), collected in hungary, were obtained by hydrodistillation. the chemical compositions of the oils were analysed by combination of gc and gc/ms. the major constituent of the oil obtained from the aerial parts of horseweed was limonene (78%), while the main component of root oil was 2z,8z-matricaria ester. the antimicrobial activities of the oils were tested on gram-positive (enterococcus faecalis, staphylococcus aureus, and strep ...201223049473
dna mutations mediate microevolution between host-adapted forms of the pathogenic fungus cryptococcus neoformans.the disease cryptococcosis, caused by the fungus cryptococcus neoformans, is acquired directly from environmental exposure rather than transmitted person-to-person. one explanation for the pathogenicity of this species is that interactions with environmental predators select for virulence. however, co-incubation of c. neoformans with amoeba can cause a "switch" from the normal yeast morphology to a pseudohyphal form, enabling fungi to survive exposure to amoeba, yet conversely reducing virulence ...201223055925
prevalence of cryptococcosis among hiv-infected patients in yaounde, cameroon.cryptococcus neoformans is encapsulated yeast which causes life-threatening infections in up to 40% of aids patients in africa.201223056017
antibacterial susceptibility patterns of blood stream isolates in patients investigated at the aga khan university hospital, nairobi.microbial invasion of the blood stream can have serious immediate consequences and are a threat to every organ in the body. timely detection and treatment is vital and necessitates hospital admission and immediate intervention.201023057259
cryptococcus albidus infection in a california sea lion (zalophus californianus).sporadic cases of cryptococcosis have been reported in marine mammals, typically due to cryptococcus neoformans and, more recently, to cryptococcus gattii in cetaceans. cryptococcus albidus, a ubiquitous fungal species not typically considered to be pathogenic, was recovered from a juvenile california sea lion (zalophus californianus) rescued near san francisco bay, california. yeast morphologically consistent with a cryptococcus sp. was identified histologically in a lymph node and c. albidus w ...201223060504
cryptococcosis.cryptococcosis is a systemic fungal infection, caused by encapsulated yeast of the genus cryptococcus, c neoformans and c gattii. these environmental microorganisms live in pigeon and other bird droppings, as well as in the fruit and bark of various trees. infection in humans and other animal species usually occurs by inhalation and less frequently through the skin and by ingestion of the fungus. most infections have a benign course and resolve spontaneously; however, the incidence of cryptococc ...201223068147
de novo gtp biosynthesis is critical for virulence of the fungal pathogen cryptococcus neoformans.we have investigated the potential of the gtp synthesis pathways as chemotherapeutic targets in the human pathogen cryptococcus neoformans, a common cause of fatal fungal meningoencephalitis. we find that de novo gtp biosynthesis, but not the alternate salvage pathway, is critical to cryptococcal dissemination and survival in vivo. loss of inosine monophosphate dehydrogenase (impdh) in the de novo pathway results in slow growth and virulence factor defects, while loss of the cognate phosphoribos ...201223071437
mechanisms of dendritic cell lysosomal killing of cryptococcus.cryptococcus neoformans is an opportunistic pulmonary fungal pathogen that disseminates to the cns causing fatal meningitis in immunocompromised patients. dendritic cells (dcs) phagocytose c. neoformans following inhalation. following uptake, cryptococci translocate to the dc lysosomal compartment and are killed by oxidative and non-oxidative mechanisms. dc lysosomal extracts kill cryptococci in vitro; however, the means of antifungal activity remain unknown. our studies determined non-oxidative ...201223074646
mechanisms of infection by the human fungal pathogen cryptococcus neoformans.brain infection by the fungus cryptococcus neoformans results in inflammation of the meninges and brain parenchyma, a condition known as meningoencephalitis. one million people are estimated to suffer cryptococcal meningitis globally and >60% of these cases die within 3 months of diagnosis. humans are believed to contract infection by inhalation of spores or dried yeast cells, which subsequently colonize the lung tissue. in the lungs, cryptococci may be cleared by the lung phagocytes, stay laten ...201223075448
the role of dendritic cells in the innate recognition of pathogenic fungi (a. fumigatus, c. neoformans and c. albicans).dendritic cells (dcs) are the bridge between the innate and adaptive immune system. dcs are responsible for sensing and patrolling the environment, initiating a host response and instructing the proper adaptive immune response against pathogens. recent advances in medical treatments have led to increased use of immunosuppressive drugs, leading to the emergence of fungal species that cause life-threatening infections in humans. three of these opportunistic fungal pathogens: aspergillus fumigatus, ...201223076328
a defect in atp-citrate lyase links acetyl-coa production, virulence factor elaboration and virulence in cryptococcus neoformans.the interaction of cryptococcus neoformans with phagocytic cells of the innate immune system is a key step in disseminated disease leading to meningoencephalitis in immunocompromised individuals. transcriptional profiling of cryptococcal cells harvested from cell culture medium or from macrophages found differential expression of metabolic and other functions during fungal adaptation to the intracellular environment. we focused on the acl1 gene for atp-citrate lyase, which converts citrate to ac ...201223078142
cryptococcus neoformans phosphoinositide-dependent kinase 1 (pdk1) ortholog is required for stress tolerance and survival in murine phagocytes.cryptococcus neoformans pkh2-01 and pkh2-02 are orthologous to mammalian pdk1 kinase genes. although orthologs of these kinases have been extensively studied in s. cerevisiae, little is known about their function in pathogenic fungi. in this study, we show that pkh2-02 but not pkh2-01 is required for c. neoformans to tolerate cell wall, oxidative, nitrosative, and antifungal drug stress. deletion of pkh2-02 leads to decreased basal levels of pkc1 activity and, consequently, reduced activation of ...201323087368
lipid raft involvement in yeast cell growth and death.the notion that cellular membranes contain distinct microdomains, acting as scaffolds for signal transduction processes, has gained considerable momentum. in particular, a class of such domains that is rich in sphingolipids and cholesterol, termed as lipid rafts, is thought to compartmentalize the plasma membrane, and to have important roles in survival and cell death signaling in mammalian cells. likewise, yeast lipid rafts are membrane domains enriched in sphingolipids and ergosterol, the yeas ...201223087902
a purified capsular polysaccharide markedly inhibits inflammatory response during endotoxic shock.capsular material of the opportunistic fungus cryptococcus neoformans is composed mainly of a polysaccharide named glucuronoxylomannan (gxm). in this study, the effects of gxm were analyzed in an in vivo experimental system of lipopolysaccharide (lps)-induced shock. endotoxic shock was induced in mice by a single intraperitoneal injection of lps from escherichia coli. gxm treatment reduced the mortality of mice at early stages. mice treated with lps alone showed markedly increased plasma levels ...201323090956
disseminated cryptococcosis in an immunocompetent child.cryptococcosis is caused by cryptococcus neoformans. immunosuppression is a predisposing factor for the development of cryptococcosis. however, reports exist that cryptococcus neoformans can cause infection in immunocompetent hosts. we report a case of disseminated cryptococcosis in a 7.5-year-old immunocompetent child.200723100931
disseminated cryptococcosis in an hiv-positive boy.cryptococcosis is rare among children, only occurring in about 1% of children with hiv. we report the case of a 12-year-old boy with disseminated cryptococcosis. he had a history of recurrent pneumonia. he then developed meningeal symptoms and was found to have disseminated cryptococcus neoformans by cerebrospinal fluid and bone marrow aspirate culture. he was treated with amphotericin b for 2 weeks (1 mg/kg/day), and then with fluconazole orally for 8 weeks (12 mg/kg/day). he also received a ne ...201223104630
systemic fungal infections in patients with human inmunodeficiency virus.histoplasmosis is a systemic infection caused by the dimorphic fungus histoplasma capsulatum. in immunocompromised patients, primary pulmonary infection can spread to the skin and meninges. clinical manifestations appear in patients with a cd4(+) lymphocyte count of less than 150 cells/μl. coccidioidomycosis is a systemic mycosis caused by coccidioides immitis and coccidioides posadasii. it can present as diffuse pulmonary disease or as a disseminated form primarily affecting the central nervous ...201423107866
immune modulation mediated by cryptococcal laccase promotes pulmonary growth and brain dissemination of virulent cryptococcus neoformans in mice.c. neoformans is a leading cause of fatal mycosis linked to cns dissemination. laccase, encoded by the lac1 gene, is an important virulence factor implicated in brain dissemination yet little is known about the mechanism(s) accounting for this observation. here, we investigated whether the presence or absence of laccase altered the local immune response in the lungs by comparing infections with the highly virulent strain, h99 (which expresses laccase) and mutant strain of h99 deficient in laccas ...201223110112
lymphocyte transformation assay for c neoformans antigen is not reliable for detecting cellular impairment in patients with neurocryptococcosis.cryptococcus neoformans causes meningitis and disseminated infection in healthy individuals, but more commonly in hosts with defective immune responses. cell-mediated immunity is an important component of the immune response to a great variety of infections, including yeast infections. we aimed to evaluate a specific lymphocyte transformation assay to cryptococcus neoformans in order to identify immunodeficiency associated to neurocryptococcosis (ncc) as primary cause of the mycosis.201223110700
meningitis admitted to a military hospital: a retrospective case series.meningitis is a common admission diagnosis. no case series or descriptive studies on meningitis have recently been published. additionally, no recent data exist on meningitis in the u.s. military health system. we reviewed charts of adult patients admitted to naval medical center san diego between january 2004 and december 2008 with an admission diagnosis of meningitis. charts were excluded if they did not meet our case definition of meningitis, if missing data, or if meningitis was nosocomial o ...201223113452
[dermatomycoses due to pets and farm animals : neglected infections?].dermatomycoses due to contact with pets and livestock frequently affect children and young adults. zoophilic dermatophytes are the main important causative agents. it has long been known that the often high inflammatory dermatophytoses of the skin and the scalp are caused mostly by microsporum canis. due to an absence of an obligation for reporting fungal infections of the skin to the public health office in germany, an unnoticed but significant change in responsible pathogens has occurred. toda ...201223114507
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
[characteristics of the eukaryotic community structure in acid mine drainage lake in anhui province, china].we characterized eukaryotic community structure and the relationship between the community structure and environmental factors in acidic mine drainage (amd) lake of a sulfide mine in anhui province, china.201223115972
1-alkyl-(n,n-dimethylamino)pyridinium bromides: inhibitory effect on virulence factors of candida albicans and on the growth of bacterial pathogens.a homologous series of 1-alkyl-(n,n-dimethylamino)pyridinium bromides, termed compounds 1-11, was synthesized and studied for antibacterial and antifungal activity. of these, compound 8, containing a ten-carbon alkyl chain, showed maximum inhibition against all the tested bacterial strains. the highest antibacterial activity using a disc diffusion method was recorded against mycobacterium smegmatis [zone of inhibition (zoi): 45.75±0.25 mm], followed by escherichia coli, proteus mirabilis, vibrio ...201323118472
successful treatment of serial opportunistic infections including disseminated nocardiosis and cryptococcal meningitis in a patient with anca-associated vasculitis.we herein present a case of serial opportunistic infections that included disseminated nocardiosis and cryptococcal meningitis in a 67-year-old man who was diagnosed with anca-associated vasculitis and treated with corticosteroids. upon admission, the initial manifestations of the disease included subcutaneous tumors and multiple lesions in the brain and lungs. nocardia farcinica was identified in a culture of the aspirated pus. the patient was successfully treated for disseminated nocardiosis w ...201223124149
cryptococcus neoformans requires the escrt protein vps23 for iron acquisition from heme, for capsule formation, and for virulence.iron availability is a key regulator of virulence factor elaboration in cryptococcus neoformans, the causative agent of fungal meningoencephalitis in hiv/aids patients. in addition, iron is an essential nutrient for pathogen proliferation in mammalian hosts but little is known about the mechanisms of iron sensing and uptake in fungal pathogens that attack humans. in this study, we mutagenized c. neoformans by agrobacterium-mediated t-dna insertion and screened for mutants with reduced growth on ...201323132495
some southern african plant species used to treat helminth infections in ethnoveterinary medicine have excellent antifungal activities.diseases caused by microorganisms and parasites remain a major challenge globally and particularly in sub-saharan africa to man and livestock. resistance to available antimicrobials and the high cost or unavailability of antimicrobials complicates matters. many rural people use plants to treat these infections. because some anthelmintics e.g. benzimidazoles also have good antifungal activity we examined the antifungal activity of extracts of 13 plant species used in southern africa to treat gast ...201223134805
new secondary metabolites from bioactive extracts of the fungus armillaria tabescens.ethyl acetate extracts of armillaria tabescens (strain jnb-oz344) showed significant fungistatic and bacteristatic activities against several major human pathogens including candida albicans, cryptococcus neoformans, escherichia coli and mycobacterium intracellulare. chemical analysis of these extracts led to the isolation and identification of four new compounds, emestrin-f (1), emestrin-g (2), 6-o-(4-o-methyl-β-d-glucopyranosyl)-8-hydroxy-2,7-dimethyl-4h-benzopyran-4-one (3) and cephalosporoli ...201323140424
cryptococcus neoformans-derived microvesicles enhance the pathogenesis of fungal brain infection.cryptococcal meningoencephalitis is the most common fungal disease in the central nervous system. the mechanisms by which cryptococcus neoformans invades the brain are largely unknown. in this study, we found that c. neoformans-derived microvesicles (cnmvs) can enhance the traversal of the blood-brain barrier (bbb) by c. neoformans invitro. the immunofluorescence imaging demonstrates that cnmvs can fuse with human brain microvascular endothelial cells (hbmecs), the constituents of the bbb. this ...201223144903
induction of brain microvascular endothelial cell urokinase expression by cryptococcus neoformans facilitates blood-brain barrier invasion.the invasive ability of the blood-borne fungal pathogen cryptococcus neoformans can be enhanced through interactions with host plasma components, such as plasminogen. previously we showed by in vitro studies that plasminogen coats the surface of c. neoformans and is converted to the active serine protease, plasmin, by host plasminogen activators. viable, but not formaldehyde- or sodium azide-killed, cryptococcal strains undergo brain microvascular endothelial cell-dependent plasminogen-to-plasmi ...201223145170
dictyostelium host response to legionella infection: strategies and assays.the professional phagocyte dictyostelium discoideum is a simple eukaryotic microorganism, whose natural habitat is deciduous forest soil and decaying leaves, where the amoebae feed on bacteria and grow as separate, independent, single cells. in the last decade, the organism has been successfully used as a host for several human pathogens, including legionella pneumophila, mycobacterium avium and mycobacterium marinum,pseudomonas aeruginosa, klebsiella pneumoniae, cryptococcus neoformans, and sal ...201323150412
a new f-actin structure in fungi: actin ring formation around the cell nucleus of cryptococcus neoformans.the f-actin cytoskeleton of cryptococcus neoformans is known to comprise actin cables, cortical patches and cytokinetic ring. here, we describe a new f-actin structure in fungi, a perinuclear f-actin collar ring around the cell nucleus, by fluorescent microscopic imaging of rhodamine phalloidin-stained f-actin. perinuclear f-actin rings form in cryptococcus neoformans treated with the microtubule inhibitor nocodazole or with the drug solvent dimethyl sulfoxide (dmso) or grown in yeast extract pe ...201323155113
chemical composition and biological activities of essential oil from hyptis crenata growing in the brazilian cerrado.essential oils from species of the genus hyptis are well-known for their significant biological properties, including antimicrobial and acaricidal activities. the essential oil from the aerial parts of h. crenata was obtained by hydrodistillation; bomeol (17.8%), 1,8-cineol (15.6%) and p-cimene (7.9%) were characterized by gc-ms as its major constituents. the essential oil was evaluated in vitro for its antimicrobial activities against six fungal and five bacterial strains, by measuring the resp ...201223157018
role of cryptococcus neoformans rho1 gtpases in the pkc1 signaling pathway in response to thermal stress.to initiate and establish infection in mammals, the opportunistic fungal pathogen cryptococcus neoformans must survive and thrive upon subjection to host temperature. primary maintenance of cell integrity is controlled through the protein kinase c1 (pkc1) signaling pathway, which is regulated by a rho1 gtpase in saccharomyces cerevisiae. we identified three c. neoformans rho gtpases, rho1, rho10, and rho11, and have begun to elucidate their role in growth and activation of the pkc1 pathway in re ...201323159519
crystal structures of acetate kinases from the eukaryotic pathogens entamoeba histolytica and cryptococcus neoformans.acetate kinases (acks) are members of the acetate and sugar kinase/hsp70/actin (askha) superfamily and catalyze the reversible phosphorylation of acetate, with adp/atp the most common phosphoryl acceptor/donor. while prokaryotic acks have been the subject of extensive biochemical and structural characterization, there is a comparative paucity of information on eukaryotic acks, and prior to this report, no structure of an ack of eukaryotic origin was available. we determined the structures of ack ...201323159802
detection of invasive fungal pathogens by real-time pcr and high-resolution melting analysis.causative agents most frequently encountered in systemic infections are bacteria, although fungi that cause invasive infections have also emerged, mostly in immune-compromised patients. the early detection and adequate treatment of bloodstream infections are critical for successful treatment. the aim of this study was to develop a rapid and efficient method for the detection and differentiation of the most common fungal pathogens.201223160681
assessment of plant lectin antifungal potential against yeasts of major importance in medical mycology.the search for new compounds with antifungal activity is accelerating due to rising yeast and fungal resistance to commonly prescribed drugs. among the molecules being investigated, plant lectins can be highlighted. the present work shows the potential of six plant lectins which were tested in vitro against yeasts of medical importance, candida albicans, candida tropicalis, candida parapsilosis, cryptococcus gattii, cryptococcus neoformans, malassezia pachydermatis, rhodotorula sp. and trichospo ...201323161017
current understanding of hog-mapk pathway in aspergillus fumigatus.aspergillus fumigatus is an important opportunistic fungal pathogen that causes lethal systemic invasive aspergillosis. it must be able to adapt to stress in the microenvironment during host invasion and systemic spread. the high-osmolarity glycerol (hog) mitogen-activated protein kinase (mapk) signaling pathway is a key element that controls adaptation to environmental stress. it plays a critical role in the virulence of several fungal pathogens. in this review, we summarize the current knowled ...201323161019
clinical utility of the cryptococcal antigen lateral flow assay in a diagnostic mycology laboratory.cryptococcus neoformans causes life-threatening meningitis. a recently introduced lateral flow immunoassay (lfa) to detect cryptococcal antigen (crag) is reportedly more rapid and convenient than standard latex agglutination (la), but has not yet been evaluated in a diagnostic laboratory setting.201223166705
the non-mammalian host galleria mellonella can be used to study the virulence of the fungal pathogen candida tropicalis and the efficacy of antifungal drugs during infection by this pathogenic yeast.although candida tropicalis is a frequent cause of invasive fungal diseases, its interaction with the host remains poorly studied. galleria mellonella is a lepidoptera model which offers a useful tool to study virulence of different microorganisms and drug efficacy. in this work we investigated the virulence of c. tropicalis in g. mellonella at different temperatures and the efficacy of antifungal drugs in this infection model. when larvae were infected with yeast inocula suspensions of differen ...201323170962
molecular characterization of the early b cell response to pulmonary cryptococcus neoformans infection.the role of b cells in host defense against fungi has been difficult to establish. we quantified and determined the molecular derivation of b-1a, b-1b, and b-2 b cell populations in c57bl/6 mice after pulmonary infection with cryptococcus neoformans. total b-1 and b-2 cell numbers increased in lungs and peritoneal cavity as early as day 1 postinfection, but lacked signs of clonal expansion. labeled capsular (24067) and acapsular (cap67) c. neoformans strains were used to identify c. neoformans-b ...201223175699
activity of the calcium channel pore cch1 is dependent on a modulatory region of the subunit mid1 in cryptococcus neoformans.calcium (ca(2+))-mediated signaling events in fungal pathogens such as cryptococcus neoformans are central to physiological processes, including those that mediate stress responses and promote virulence. the cch1-mid1 channel (cmc) represents the only high-affinity ca(2+) channel in the plasma membrane of fungal cells; consequently, cryptococci cannot survive in low-ca(2+) environments in the absence of cmc. previous electrophysiological characterization revealed that cch1, the predicted channel ...201323175710
a limited role of inkt cells in controlling systemic candida albicans infections.candida albicans is a major cause of invasive fungal infections. mortality attributable to candidemia is very high, even when patients are treated with adequate antifungal agents. therefore, it is important to investigate the mechanisms of immune response to c. albicans. invariant natural killer t (inkt) cells, innate lymphocytes that express an invariant t cell receptor α chain, participate in the response to various microbes, including two fungal pathogens, aspergillus fumigatus and cryptococc ...201223183205
aimless mutants of cryptococcus neoformans: failure to disseminate.the pathogenic fungus cryptococcus neoformans exhibits a striking propensity to cause central nervous system (cns) disease in people with hiv/aids. given that cryptococcal infections are generally initiated by pulmonary colonization, dissemination requires that the fungus withstand phagocytic killing, cross the alveolar-capillary interface in the lung, survive in the circulatory system and breach the blood-brain barrier. we know little about the molecular mechanisms underlying dissemination, but ...201223189087
antimicrobial activities of endophytic fungi isolated from ophiopogon japonicus (liliaceae).drug resistance in bacteria has become a global concern and the search for new antibacterial agents is urgent and ongoing. endophytes provide an abundant reservoir of bioactive metabolites for medicinal exploitation, and an increasing number of novel compounds are being isolated from endophytic fungi. ophiopogon japonicus, containing compounds with antibacterial activity, is a traditional chinese medicinal plant used for eliminating phlegm, relieving coughs, latent heat in the lungs, and allevia ...201223190550
antifolates inhibit cryptococcus biofilms and enhance susceptibility of planktonic cells to amphotericin b.the cryptococcus neoformans species complex contains the most important agents of fungal meningoencephalitis. therapeutic choices are limited and issues related to toxicity and resistance to antifungals have been described. the present study evaluated the inhibitory effect of the antifolate combinations sulfamethoxazole-trimethoprim (smx/tmp) and sulfadiazine-pyrimethamine (sdz/pyr) against planktonic cells and biofilms of c. neoformans and c. gattii. the influence of the antifolate combinations ...201323192488
chronic suppurative cryptococcal extensor tenosynovitis in a patient with castleman's disease: a case report.cryptococcus neoformans is an ubiquitously occurring encapsulated fungus that is commonly found in the environment. it is also an opportunistic pathogen that has potential to cause systemic fungal infection, predominantly in the immunocompromised host with cell-mediated immunological defects. cryptococcal tenosynovitis is an extremely rare condition, with only a few cases previously documented in the literature. we report a case of chronic suppurative cryptococcal extensor tenosynovitis in a pat ...201123204976
central nervous system cryptococcosis among a cohort of hiv infected patients from a university hospital of north india.cryptococcus neoformans is a ubiquitous encapsulated yeast that causes significant infections which range from asymptomatic pulmonary colonization to the life threatening meningoencephalitis, especially in immunocompromised individuals. cryptococcal meningitis is one of the aids-defining illnesses. recent data have indicated that, the incidence of the cryptococcal infection is high in developing countries like india. we conducted this study to find out the incidence of cryptococcosis in this are ...201223205353
depletion of neutrophils in a protective model of pulmonary cryptococcosis results in increased il-17a production by γδ t cells.protective responses in mice immunized with an interferon-gamma producing strain of cryptococcus neoformans, h99γ, are associated with il-17a production by neutrophils. neutrophil depletion in h99γ-immunized mice did not affect pulmonary fungal burden, indicating that neutrophils are not required for clearance. however, we observed an increase in il-17a in the lungs of neutrophil-depleted h99γ infected mice, which corresponded to an increase in il-17a+ γδ+ t cells. moreover, we observed increase ...201223216912
a human fungal pathogen cryptococcus neoformans expresses three distinct iron permease homologs.iron plays a key role in host-pathogen interactions. microbial pathogens require iron for survival and virulence, whereas mammalian hosts sequester and withhold iron as a means of nutritional immunity. we previously identified two paralogous genes, cft1 and cft2, which encode homologs of a fungal iron permease, cft1 and cft2, respectively, in the human fungal pathogen cryptococcus neoformans. cft1 was shown to play a role in the high-affinity reductive iron uptake system, and was required for tr ...201223221526
antibody binding to cryptococcus neoformans impairs budding by altering capsular mechanical properties.abs to microbial capsules are critical for host defense against encapsulated pathogens, but very little is known about the effects of ab binding on the capsule, apart from producing qualitative capsular reactions ("quellung" effects). a problem in studying ab-capsule interactions is the lack of experimental methodology, given that capsules are fragile, highly hydrated structures. in this study, we pioneered the use of optical tweezers microscopy to study ab-capsule interactions. binding of prote ...201323233725
flavodonfuran: a new difuranylmethane derivative from the mangrove endophytic fungus flavodon flavus psu-ma201.one new difuranylmethane derivative, flavodonfuran (1), together with tremulenolide a (2) was isolated from the mangrove-derived fungus flavodon flavus psu-ma201.the difuranylmethane derivative based on 1 is rare in natural products. their structures were established by spectroscopic evidence. compound 2 exhibited mild antibacterial and antifungal activities against staphylococcus aureus atcc25923 and cryptococcus neoformans atcc90113, respectively.201323234367
a mistaken diagnosis of molluscum contagiosum in a hiv-positive patient in rural south africa.a 25-year-old gentleman presented with multiple small ulcerations and papules covering a large portion of his face and neck, associated with general malaise. he was hiv seropositive with a total cd4 count of 78 cells/µl. a diagnosis of molluscum contagiosum was made and the patient discharged. he re-presented 3 weeks later with a 2-day history of progressively worsening headache associated with photophobia and diarrhoea. the generalised skin eruption had worsened, now involving his torso and upp ...201223242094
a repurposing approach identifies off-patent drugs with fungicidal cryptococcal activity, a common structural chemotype, and pharmacological properties relevant to the treatment of cryptococcosis.new, more accessible therapies for cryptococcosis represent an unmet clinical need of global importance. we took a repurposing approach to identify previously developed drugs with fungicidal activity toward cryptococcus neoformans, using a high-throughput screening assay designed to detect drugs that directly kill fungi. from a set of 1,120 off-patent medications and bioactive molecules, we identified 31 drugs/molecules with fungicidal activity, including 15 drugs for which direct antifungal act ...201323243064
the crz1/sp1 transcription factor of cryptococcus neoformans is activated by calcineurin and regulates cell wall integrity.cryptococcus neoformans survives host temperature and regulates cell wall integrity via a calcium-dependent phosphatase, calcineurin. however, downstream effectors of c. neoformans calcineurin are largely unknown. in s. cerevisiae and other fungal species, a calcineurin-dependent transcription factor crz1, translocates to nuclei upon activation and triggers expression of target genes. we now show that the c. neoformans crz1 ortholog (crz1/sp1), previously identified as a protein kinase c target ...201223251520
Refresh
firstprev
...61626364656667686970...
nextlast
Displaying items 6501 - 6600 of 7882