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discovery of highly potent triazole antifungal derivatives by heterocycle-benzene bioisosteric replacement.on the basis of our previously discovered triazole antifungal lead compounds, heterocycle-benzene bioisosteric replacement was used to improve their pharmacokinetic profile. the designed new triazole derivatives have good antifungal activity toward a wide range of pathogenic fungi. their binding mode with the target enzyme was clarified by molecular docking. the mic value of the highly potent compound 8f against candida albicans, candida tropicalis, and cryptococcus neoformans is 0.016 μg/ml, 0. ...201323643831
an opportunistic infection associated with ruxolitinib, a novel janus kinase 1,2 inhibitor.we report a case of cryptococcus neoformans pneumonia in a patient taking ruxolitinib, a janus kinase 1,2 inhibitor approved for the treatment of myelofibrosis. we hypothesize that ruxolitinib contributed to this infection through its effects on cell-mediated immunity. clinicians should be aware of the potential for intracellular or opportunistic infections associated with this novel drug class.201323648912
fluconazole for the treatment of cryptococcus neoformans meningitis in an immunocompetent host.we present a case of a 23-year-old immunocompetent male who presented with chronic meningitis and was diagnosed as cryptococcal meningitis by positive cryptococcal antigen titer. the cerebrospinal fluid culture was positive for cryptococcus neoformans. he was treated initially with amphotericin b but was later changed to fluconazole due to toxicity. this case highlights the use of fluconazole to successfully treat chronic meningitis in an immunocompetent host.200323649032
cryptococcus lacticolor sp. nov. and rhodotorula oligophaga sp. nov., novel yeasts isolated from the nasal smear microbiota of queensland koalas kept in japanese zoological parks.a total of 515 yeast strains were isolated from the nasal smears of queensland koalas and their breeding environments in japanese zoological parks between 2005 and 2012. the most frequent species in the basidiomycetous yeast biota isolated from koala nasal passages was cryptococcus neoformans, followed by rhodotorula minuta. r. minuta was the most frequent species in the breeding environments, while c. neoformans was rare. seven strains representing two novel yeast species were identified. analy ...201323653119
factors required for activation of urease as a virulence determinant in cryptococcus neoformans.urease in cryptococcus neoformans plays an important role in fungal dissemination to the brain and causing meningoencephalitis. although urea is not required for synthesis of apourease encoded by ure1, the available nitrogen source affected the expression of ure1 as well as the level of the enzyme activity. activation of the apoenzyme requires three accessory proteins, ure4, ure6, and ure7, which are homologs of the bacterial urease accessory proteins ured, uref, and ureg, respectively. a yeast ...201323653445
multicenter study evaluating the vitek ms system for identification of medically important yeasts.the optimal management of fungal infections is correlated with timely organism identification. matrix-assisted laser desorption ionization-time of flight (maldi-tof) mass spectrometry (ms) is revolutionizing the identification of yeasts isolated from clinical specimens. we present a multicenter study assessing the performance of the vitek ms system (biomérieux) in identifying medically important yeasts. a collection of 852 isolates was tested, including 20 candida species (626 isolates, includin ...201323658267
the production of monokaryotic hyphae by cryptococcus neoformans can be induced by high temperature arrest of the cell cycle and is independent of same-sex mating.cryptococcus neoformans is a heterothallic fungal pathogen of humans and animals. although the fungus grows primarily as a yeast, hyphae are produced during the sexual phase and during a process called monokaryotic fruiting, which is also believed to involve sexual reproduction, but between cells of the same mating type. here we report a novel monokaryotic fruiting mechanism that is dependent on the cell cycle and occurs in haploid cells in the absence of sexual reproduction. cells grown at 37°c ...201323658522
uncoupling of mrna synthesis and degradation impairs adaptation to host temperature in cryptococcus neoformans.the pathogenic fungus cryptococcus neoformans must overcome multiple stressors to cause disease in its human host. in this study, we report that c. neoformans rapidly and transiently repressed ribosomal protein (rp) transcripts during a transition from 30°c to host temperature. this repression was accompanied by accelerated mrna degradation mediated by the major deadenylase, ccr4, and influenced by the dissociable rna polymerase ii subunit, rpb4. destabilization and deadenylation of rp transcrip ...201323659661
evaluation of pharmacological activities, cytotoxicity and phenolic composition of four maytenus species used in southern african traditional medicine to treat intestinal infections and diarrhoeal diseases.microbial infections and resulting inflammation and oxidative stress are common pathogenesis of gastrointestinal tract (git) disorders. in south africa, several species of the genus maytenus are used in traditional medicine to treat various infectious diseases. most of the previous work on this genus was focused on nonpolar extracts from the root and bark. in this study, leaf extracts of polar extracts of maytenus peduncularis, maytenus procumbens, maytenus senegalensis and maytenus undata were ...201323663902
characterization of the complete uric acid degradation pathway in the fungal pathogen cryptococcus neoformans.degradation of purines to uric acid is generally conserved among organisms, however, the end product of uric acid degradation varies from species to species depending on the presence of active catabolic enzymes. in humans, most higher primates and birds, the urate oxidase gene is non-functional and hence uric acid is not further broken down. uric acid in human blood plasma serves as an antioxidant and an immune enhancer; conversely, excessive amounts cause the common affliction gout. in contrast ...201323667704
congenic strains for genetic analysis of virulence traits in cryptococcus gattii.cryptococcus gattii is responsible for a large outbreak of potentially fatal disease that started in the late 1990s on vancouver island, canada. how this fungus and the outbreak isolates in particular cause disease in immunocompetent people is unknown, with differing hypotheses. to explore genetic contributions, a pair of congenic a and α mating type strains was generated by a series of 11 backcrosses to introgress the mat locus from a nonoutbreak strain into the background of strain r265, isola ...201323670558
congenic strains of the filamentous form of cryptococcus neoformans for studies of fungal morphogenesis and virulence.cryptococcus neoformans is an unconventional dimorphic fungus that can grow either as a yeast or in a filamentous form. to facilitate investigation of genetic factors important for its morphogenesis and pathogenicity, congenic a and α strains for a filamentous form were constructed. xl280 (α) was selected as the background strain because of its robust ability to undergo the morphological transition from yeast to the filamentous form. the mata allele from a sequenced strain jec20 was introgressed ...201323670559
cryptococcal meningitis accompanying lymphocytic inflammation predominantly in cerebral deep white matter: a possible manifestation of immune reconstitution inflammatory syndrome.cryptococcal meningitis is rarely complicated by immune-mediated leukoencephalopathy, but the precise pathomechanism is uncertain. a 72-year-old japanese man treated with prednisolone for sweet disease developed a subacute progression of meningitis, which was considered as neuro-sweet disease. a treatment by methylprednisolone rapidly improved csf findings with a remarkable decrease in lymphocyte numbers in the blood, but the patient's consciousness still worsened after the cessation of the trea ...201423683170
antimicrobial activity of schinus lentiscifolius (anacardiaceae).schinus lentiscifolius marchand (syn. schinus weinmannifolius engl) is a plant native to rio grande do sul (southern brazil) and has been used in brazilian traditional medicine as antiseptic and antimicrobial for the treatment of many different health problems as well as to treat leucorrhea and to assist in ulcer and wound healing. although it is a plant widely used by the population, there are no studies proving this popular use.201323684720
antimicrobial activity and cytotoxicity of triterpenes isolated from leaves of maytenus undata (celastraceae).plants of the genus maytenus belong to the family celastraceae and are widely used in folk medicine as anti-tumour, anti-asthmatic, analgesic, anti-inflammatory, antimicrobial and anti-ulcer agents, and as a treatment for stomach problems. the aim of this study was to isolate and identify active compounds with antifungal activity from maytenus undata after a preliminary study highlighted promising activity in crude extracts.201323688235
evidence for mitotic recombination within the basidia of a hybrid cross of cryptococcus neoformans.in the majority of diploid eukaryotes, each meiotic process generates four haploid gametes with each containing a single recombinant nucleus. in some species and/or some meiotic processes, aneuploid or diploid gametes can also be generated due to chromosomal non-disjunction and/or the co-packaging of two of the four haploid nuclei into the same gamete. here we show that another process is involved in generating genotypes of sexual progeny from a hybrid cross between two divergent lineages of the ...201323690954
the glucose sensor-like protein hxs1 is a high-affinity glucose transporter and required for virulence in cryptococcus neoformans.cryptococcus is a major fungal pathogen that frequently causes systemic infection in patients with compromised immunity. glucose, an important signal molecule and the preferred carbon source for cryptococcus, plays a critical role in fungal development and virulence. cryptococcus contains more than 50 genes sharing high sequence homology with hexose transporters in saccharomyces cerevisiae. however, there is no report on their function in glucose sensing or transport. in this study, we investiga ...201323691177
histopathological study of murine pulmonary cryptococcosis induced by cryptococcus gattii and cryptococcus neoformans.although cryptococcus gattii can cause life-threatening complications, putative virulence factors of c. gattii remain controversial. therefore, we conducted the present study to elucidate the virulence factors of the yeast and found that the mortality rate of mice infected with c. gattii r265 was significantly higher than that of those infected with c. gattii 5815; however, no difference was found in the mortality rates between mice infected with c. gattii r265 and cryptococcus neoformans h99. i ...201323698482
nitrogen regulation of virulence in clinically prevalent fungal pathogens.the habitats of fungal pathogens range from environmental to commensal, and the nutrient content of these different niches varies considerably. upon infection of humans, nutrient availability changes significantly depending on the site and pathophysiology of infection. nonetheless, a common feature enabling successful establishment in these niches is the ability to metabolise available nutrients including sources of nitrogen, carbon and essential metals such as iron. in particular, nitrogen sour ...201323701678
pseudo-subarachnoid hemorrhage in cryptococcal meningitis: mri findings and pathological study.a pseudo-subarachnoid hemorrhage (pseudo-sah) is a brain computed tomography (ct) finding that is seen as high-density areas along the basal cisterns, the sylvian vallecula/fissure, the tentorium cerebella, or the cortical sulci, although no sah is found upon lumbar puncture or at autopsy. there is one report of cryptococcal meningitis presenting as pseudo-sah, but the explanatory pathology is unknown. a 68-year-old woman with headache, fever, decreased hearing, and decreased vision was admitted ...201323703398
clinical characteristics and risk factors of non-candida fungaemia.the incidence of fungaemia has been increasing worldwide. it is important to distinguish non-candida fungaemia from candidaemia because of their different antifungal susceptibilities. the aims of this study were to investigate the clinical characteristics of non-candida fungaemia and identify the clinical factors that differentiate it from candidaemia.201323714136
echinocandin and triazole antifungal susceptibility profiles for clinical opportunistic yeast and mold isolates collected from 2010 to 2011: application of new clsi clinical breakpoints and epidemiological cutoff values for characterization of geographic and temporal trends of antifungal resistance.the sentry antimicrobial surveillance program monitors global susceptibility and resistance rates of newer and established antifungal agents. we report the echinocandin and triazole antifungal susceptibility patterns for 3,418 contemporary clinical isolates of yeasts and molds. the isolates were obtained from 98 laboratories in 34 countries during 2010 and 2011. yeasts not presumptively identified by chromagar, the trehalose test, or growth at 42°c and all molds were sequence identified using in ...201323720791
neurovirulence of cryptococcus neoformans determined by time course of capsule accumulation and total volume of capsule in the brain.cryptococcal meningitis remains a significant opportunistic infection in hiv-infected individuals worldwide, despite availability of antiretroviral therapies in developed nations. current therapy with amphotericin b is difficult to administer and only partially effective. mechanisms of cryptococcal neuropathogenesis are still not clearly defined. in the present study, we used a c57bl/6 mouse model with intravenous inoculation of three isogenic strains of cryptococcus neoformans: h99, cap59, and ...201323733307
scavenger receptor a modulates the immune response to pulmonary cryptococcus neoformans infection.scavenger receptors represent an important class of pattern recognition receptors shown to mediate both beneficial and detrimental roles in host defense against microbial pathogens. the role of the major macrophage scavenger receptor, scavenger receptor a (sra), in the immune response against the pathogenic fungus, cryptococcus neoformans, is unknown. to evaluate the role of sra in anticryptococcal host defenses, sra(+/+) mice and sra(-/-) mice were infected intratracheally with c. neoformans. r ...201323733871
toll-like receptor stimulation increases phagocytosis of cryptococcus neoformans by microglial cells.toll-like receptors (tlrs) belong to the family of pattern-recognition receptors with a crucial function of recognising pathogen-associated molecular patterns (pamps). cryptococcal meningitis is a potentially fatal disease with a high mortality and risk of neurological sequelae.201323738865
in vitro activities of isavuconazole and comparator antifungal agents tested against a global collection of opportunistic yeasts and molds.isavuconazole is a new broad-spectrum triazole with a favorable pharmacokinetic and safety profile. we report the mic distributions for isavuconazole and 111 isolates of candida (42 candida albicans, 25 candida glabrata, 22 candida parapsilosis, 14 candida tropicalis, and 8 candida krusei isolates), as determined by clinical and laboratory standards institute (clsi) and european committee on antimicrobial susceptibility testing (eucast) broth microdilution (bmd) methods. also, the relative activ ...201323740727
the role of host gender in the pathogenesis of cryptococcus neoformans infections.cryptococcus neoformans (cn) is a pathogenic yeast and the cause of cryptococcal meningitis. prevalence of disease between males and females is skewed, with males having an increased incidence of disease. based on the reported gender susceptibility differences to cn in the literature, we used clinical isolates from botswanan hiv-infected patients to test the hypothesis that different gender environments exerted different selective pressures on cn. when we examined this data set, we found that me ...201323741297
structural determinants of oligomerization of δ(1)-pyrroline-5-carboxylate dehydrogenase: identification of a hexamerization hot spot.the aldehyde dehydrogenase (aldh) superfamily member δ(1)-pyrroline-5-carboxylate dehydrogenase (p5cdh) catalyzes the nad(+)-dependent oxidation of glutamate semialdehyde to glutamate, which is the final step of proline catabolism. defects in p5cdh activity lead to the metabolic disorder type ii hyperprolinemia, p5cdh is essential for virulence of the fungal pathogen cryptococcus neoformans, and bacterial p5cdhs have been targeted for vaccine development. although the enzyme oligomeric state is ...201323747974
two rac paralogs regulate polarized growth in the human fungal pathogen cryptococcus neoformans.a genome wide analysis of the human fungal pathogen cryptococcus neoformans var. grubii has revealed a number of duplications of highly conserved genes involved in morphogenesis. previously, we reported that duplicate cdc42 paralogs provide c. neoformans with niche-specific responses to environmental stresses: cdc42 is required for thermotolerance, while cdc420 supports the formation of titan cells. the related rho-gtpase rac1 has been shown in c. neoformans var. neoformans to play a major role ...201323748012
cryptococcal encephalopathy without persisting cerebrospinal fluid pleocytosis, a diagnostic challenge: case report and review of the literature. 201323756084
candida albicans: a model organism for studying fungal pathogens.candida albicans is an opportunistic human fungal pathogen that causes candidiasis. as healthcare has been improved worldwide, the number of immunocompromised patients has been increased to a greater extent and they are highly susceptible to various pathogenic microbes and c. albicans has been prominent among the fungal pathogens. the complete genome sequence of this pathogen is now available and has been extremely useful for the identification of repertoire of genes present in this pathogen. th ...201223762753
global transcriptome analysis of eukaryotic genes affected by gromwell extract.gromwell is known to have diverse pharmacological, cosmetic and nutritional benefits for humans. nevertheless, the biological influence of gromwell extract (ge) on the general physiology of eukaryotic cells remains unknown. in this study a global transcriptome analysis was performed to identify genes affected by the addition of ge with cryptococcus neoformans as the model system.201423765595
histidine phosphotransfer proteins in fungal two-component signal transduction pathways.the histidine phosphotransfer (hpt) protein ypd1 is an important participant in the saccharomyces cerevisiae multistep two-component signal transduction pathway and, unlike the expanded histidine kinase gene family, is encoded by a single gene in nearly all model and pathogenic fungi. ypd1 is essential for viability in both s. cerevisiae and in cryptococcus neoformans. these and other aspects of ypd1 biology, combined with the availability of structural and mutational data in s. cerevisiae, sugg ...201323771905
hiv and co-infections.despite significant reductions in morbidity and mortality secondary to availability of effective combination anti-retroviral therapy (cart), human immunodeficiency virus (hiv) infection still accounts for 1.5 million deaths annually. the majority of deaths occur in sub-saharan africa where rates of opportunistic co-infections are disproportionately high. in this review, we discuss the immunopathogenesis of five common infections that cause significant morbidity in hiv-infected patients globally. ...201323772618
cryptococcus neoformans promotes its transmigration into the central nervous system by inducing molecular and cellular changes in brain endothelial cells.cryptococcus spp. cause fungal meningitis, a life-threatening infection that occurs predominately in immunocompromised individuals. in order for cryptococcus neoformans to invade the central nervous system (cns), it must first penetrate the brain endothelium, also known as the blood-brain barrier (bbb). despite the importance of the interrelation between c. neoformans and the brain endothelium in establishing cns infection, very little is known about this microenvironment. here we sought to reso ...201323774597
cryptococcal meningitis: description of 3 cases and estimation of t-cell subsets.to describe three cases of cryptococcus neoformans meningitis and evaluate their cellular immunity.201423775204
isolated cryptococcal osteomyelitis in an immune-competent host: a case report.cryptococcus neoformans is a ubiquitous organism that often causes opportunistic infections in immune-compromised patients. the pulmonary and central nervous systems are most commonly affected. osseous involvement is infrequent and is usually associated with disseminated systemic infection. isolated cryptococcal osteomyelitis is exceedingly rare. we report the case of a 56-year-old immunocompetent man who presented with isolated cryptococcal osteomyelitis of the humerus.201323777597
kb425796-a, a novel antifungal antibiotic produced by paenibacillus sp. 530603.the novel antifungal macrocyclic lipopeptidolactone, kb425796-a (1), was isolated from the fermentation broth of bacterial strain 530603, which was identified as a new paenibacillus species based on morphological and physiological characteristics, and 16s rrna sequences. kb425796-a (1) was isolated as white powder by solvent extraction, hp-20 and ods-b column chromatography, and lyophilization, and was determined to have the molecular formula c79h115n19o18. kb425796-a (1) showed antifungal activ ...201323778117
macrophage m1/m2 polarization dynamically adapts to changes in cytokine microenvironments in cryptococcus neoformans infection.the outcome of cryptococcal pneumonia correlates with local macrophage polarization status, as m1 and m2 polarization marks protective and nonprotective responses, respectively. overall, pulmonary macrophage polarization status changes over time during a cryptococcal infection. this could have been caused by repolarization of individual macrophages or by a replacement of m2-polarized cells by new m1-polarized cells. to explore the ability of macrophages to change between polarization states, we ...201323781069
unisexual reproduction enhances fungal competitiveness by promoting habitat exploration via hyphal growth and sporulation.unisexual reproduction is a novel homothallic sexual cycle recently discovered in both ascomycetous and basidiomycetous pathogenic fungi. it is a form of selfing that induces the yeast-to-hyphal dimorphic transition in isolates of the α mating type of the human fungal pathogen cryptococcus neoformans. unisexual reproduction may benefit the pathogen by facilitating sexual reproduction in the absence of the opposite a mating type and by generating infectious propagules called basidiospores. here, ...201323794511
fungal adhesion protein guides community behaviors and autoinduction in a paracrine manner.microbes live mostly in a social community rather than in a planktonic state. such communities have complex spatiotemporal patterns that require intercellular communication to coordinate gene expression. here, we demonstrate that cryptococcus neoformans, a model eukaryotic pathogen, responds to an extracellular signal in constructing its colony morphology. the signal that directs this community behavior is not a molecule of low molecular weight like pheromones or quorum-sensing molecules but a s ...201323798436
is the nickel-dependent urease complex of cryptococcus the pathogen's achilles' heel?the nitrogen-scavenging enzyme urease has been coopted in a variety of pathogenic organisms as a virulence factor, most notoriously to neutralize stomach acid and establish infection by the gastric pathogen helicobacter pylori. the opportunistic fungal pathogen cryptococcus neoformans also utilizes urease as a virulence factor, only in this case to invade the central nervous system (cns) via the blood-brain barrier and cause life-threatening meningoencephalitis. a recent study [a. singh, r. pant ...201323800398
a novel amalgamation of 1,2,3-triazoles, piperidines and thieno pyridine rings and evaluation of their antifungal activity.it is the first report of the novel amalgamation of 1,2,3-triazoles, piperidines, thieno pyridine rings and evaluation of their antifungal activity. the synthesized compounds showed interesting moderate to good antifungal activity, wherein they were able to discriminate between the two species aspergillus flavus and aspergillus niger of the same genus. in addition, the main highlight of this series is the sensitivity of the fungal strain cryptococcus neoformans to the compounds having p-chlorobe ...201323807083
determination of the minimum inhibitory concentration of cryptococcus neoformans and cryptococcus gattii against fluconazole by flow cytometry.recent studies have used flow cytometry (fcm) as an important alternative method to determine the antifungal susceptibility of yeasts compared to the broth microdilution clinical and laboratory standards institute (clsi) reference procedure. we present a comparative study of the broth microdilution method and flow cytometry to assess the in vitro antifungal susceptibility of cryptococcus neoformans (n = 16) and c. gattii (n = 24) to fluconazole. the minimum inhibitory concentration (mic) assays ...201423808405
chest radiography for predicting the cause of febrile illness among inpatients in moshi, tanzania.to describe chest radiographic abnormalities and assess their usefulness for predicting causes of fever in a resource-limited setting.201323809268
an encapsulation of iron homeostasis and virulence in cryptococcus neoformans.vertebrate hosts actively sequester iron, and fungal and other pathogens must therefore adapt to a severe limitation in iron availability to cause disease. recent studies reveal that the pathogenic fungus cryptococcus neoformans overcomes iron limitation by multiple mechanisms that target transferrin and heme. the regulation of iron uptake is mediated by an interconnected set of transcription factors that include the master iron regulator cir1 and the ph-responsive factor rim101. these factors i ...201323810126
native trees of the northeast argentine: natural hosts of the cryptococcus neoformans-cryptococcus gattii species complex.in argentina, information about epidemiology and environmental distribution of cryptococcus is scarce. the city of resistencia borders with brazil and paraguay where this fungus is endemic. all these supported the need to investigate the ecology of the genus and the epidemiology of cryptococcosis in this area.201423810786
bioassay-guided fractionation of extracts from hypericum perforatum in vitro roots treated with carboxymethylchitosans and determination of antifungal activity against human fungal pathogens.the aim of this study was to individuate, by bioassay-guided fractionation, promising antifungal fractions and/or constituents from hypericum perforatum subsp. angustifolium in vitro roots. treatments with chitosan, o-carboxymethylchitosan (cmc) and its derivatives were used to improve xanthone production in the roots. the bioassay-guided fractionation of cmc-treated roots led to the individuation of an ethyl acetate fraction, containing the highest amount of xanthones (6.8%) and showing the bes ...201323811777
a high-throughput screening assay for assessing the viability of cryptococcus neoformans under nutrient starvation conditions.cryptococcus neoformans causes an estimated 600,000 aids-related deaths annually that occur primarily in resource-limited countries. fluconazole and amphotericin b are currently available for the treatment of cryptococcal-related infections. however, fluconazole has limited clinical efficacy and amphotericin b requires intravenous infusion and is associated with high renal toxicity. therefore, there is an unmet need for a new orally administrable anti-cryptococcal drug. we have developed a high- ...201323812880
cryptococcosis in cats: abcd guidelines on prevention and management.cryptococcosis is worldwide the most common systemic fungal disease in cats; it is caused by the cryptococcus neoformans- cryptococcus gattii species complex, which includes eight genotypes and some subtypes (strains) with varying geographical distribution, pathogenicity and antimicrobial susceptibility. cats acquire the infection from a contaminated environment. the prognosis is favourable in most cases, provided a diagnosis is obtained sufficiently early and prolonged treatment is maintained.201323813826
x-linked immunodeficient mice exhibit enhanced susceptibility to cryptococcus neoformans infection.abstract bruton's tyrosine kinase (btk) is a signaling molecule that plays important roles in b-1 b cell development and innate myeloid cell functions and has recently been identified as a target for therapy of b cell lymphomas. we examined the contribution of b-1 b cells to resistance to cryptococcus neoformans infection by utilizing x-linked immunodeficient (xid) mice (cba-cahn-xid), which possess a mutation in btk. xid mice had significantly higher brain fungal burdens than the controls 6 wee ...201323820392
hippolachnin a, a new antifungal polyketide from the south china sea sponge hippospongia lachne.hippolachnin a (1), a polyketide possessing an unprecedented carbon skeleton with a four-membered ring, was isolated from the south china sea sponge hippospongia lachne. the structure was elucidated using ms and nmr spectroscopic analyses, and the absolute configuration was determined using a calculated ecd method. hippolachnin a demonstrated potent antifungal activity against three pathogenic fungi, cryptococcus neoformans, trichophyton rubrum, and microsporum gypseum, with a mic value of 0.41 ...201323829334
azole heteroresistance in cryptococcus neoformans: emergence of resistant clones with chromosomal disomy in the mouse brain during fluconazole treatment.we have previously reported that cryptococcus neoformans strains are innately heteroresistant to fluconazole in vitro, producing minor, highly resistant subpopulations due to adaptive formation of disomic chromosomes. using a mouse model, we assessed the emergence of heteroresistant clones in the brain during fluconazole treatment and found that the occurrence of heteroresistant clones in vivo with chromosomal disomy is strain dependent. interestingly, emergence of heteroresistant clones in vivo ...201323836187
cryptococcus neoformans pericarditis associated with hodgkin's disease. 196623841205
first molecular typing of cryptococcemia-causing cryptococcus in central-west brazil.molecular epidemiology studies on cryptococcemia are limited. this study aimed to describe the clinical features of patients with bloodstream infections by cryptococcus sp. in a public tertiary hospital in mato grosso do sul, as well as identify the fungus' molecular type and determine its antifungal susceptibility. molecular typing was performed using ura5 restriction fragment length polymorphism pcr, and antifungal susceptibility was determined by microdilution method standardized by the clini ...201323846587
genotypic diversity of environmental cryptococcus neoformans isolates from northern portugal.the cryptococcus neoformans/c. gattii species complex members are the main agents of systemic cryptococcosis. this disease is believed to be acquired from the environment via fungal cell inhalation. often, isolates recovered from environmental and clinical sources have proven to be genotypically similar. we assessed the occurrence of c. neoformans and c. gattii in environmental substrates collected in a portuguese region. twenty-eight isolates were identified as c. neoformans - five from decayin ...201423848429
phosphoproteome of cryptococcus neoformans.cryptococcus neoformans is an encapsulated pathogenic yeast, which causes life threatening meningitis in immunocompromised individuals. c. neoformans var. grubii is the most prevalent and virulent form among the two varieties of c. neoformans - c. neoformans var. grubii and c. neoformans var. neoformans. the virulence of c. neoformans is mainly conferred by its capsule and melanin. camp dependent pka-induced phosphorylation events are reported to be associated with the expression of these virule ...201423851311
use of image cytometry for quantification of pathogenic fungi in association with host cells.studies of the cellular pathogenesis mechanisms of pathogenic yeasts such as candida albicans, histoplasma capsulatum, and cryptococcus neoformans commonly employ infection of mammalian hosts or host cells (i.e. macrophages) followed by yeast quantification using colony forming unit analysis or flow cytometry. while colony forming unit enumeration has been the most commonly used method in the field, this technique has disadvantages and limitations, including slow growth of some fungal species on ...201323851941
an acidic microenvironment increases nk cell killing of cryptococcus neoformans and cryptococcus gattii by enhancing perforin degranulation.cryptococcus gattii and cryptococcus neoformans are encapsulated yeasts that can produce a solid tumor-like mass or cryptococcoma. analogous to malignant tumors, the microenvironment deep within a cryptococcoma is acidic, which presents unique challenges to host defense. analogous to malignant cells, nk cells kill cryptococcus. thus, as in tumor defense, nk cells must kill yeast cells across a gradient from physiologic ph to less than 6 in the center of the cryptococcoma. as acidic ph inhibits a ...201323853583
clinical and microbiological features of cryptococcal meningitis.in this study, the clinical features, underlying diseases and clinical outcomes of patients with cryptococcosis were investigated. in addition, a molecular analysis of the cryptococcus neoformans species complex isolated from these patients was performed.201323856876
role of narrowband imaging in assessing endobronchial cryptococcosis.endobronchial cryptococcosis can cause tracheobronchitis with granulomatous changes. in this patient under steroid therapy, bronchoscopic images revealed elevated white patchy lesion on the posterior longitudinal folds of the lower trachea. bronchoscopy with narrowband imaging (nbi) revealed opaque bronchial subepithelial vessels. endobronchial biopsy confirmed cryptococcus neoformans infection in the subepithelial layer. following treatment with fluconazole, bronchoscopy with nbi revealed the d ...201323857200
[cryptococcosis: case reports, epidemiology and treatment options].cryptococcosis is a fungal infection that is usually caused by cryptococcus neoformans. given the decreasing number of cases in hiv-infected patients in developed countries, infections in other patient populations, such as solid organ transplant recipients, patients with chronic organ diseases or even patients without immunodeficiency gain more attention. due to a possible involvement of many organs, the clinical presentation varies from localized infections of the respiratory tract and the skin ...201323860684
invasive fungal infections in argentine patients with systemic lupus erythematosus.infections are the leading cause of morbidity and mortality in patients with systemic lupus erythematosus (sle). invasive fungal infections (ifi) comprise a group of diseases caused by cryptococcus, histoplasma, aspergillus and candida. few studies of ifi have been published in patients with sle and associated factors have not been completely defined.201323861029
molecular epidemiology reveals genetic diversity amongst isolates of the cryptococcus neoformans/c. gattii species complex in thailand.to gain a more detailed picture of cryptococcosis in thailand, a retrospective study of 498 c. neoformans and c. gattii isolates has been conducted. among these, 386, 83 and 29 strains were from clinical, environmental and veterinary sources, respectively. a total of 485 c. neoformans and 13 c. gattii strains were studied. the majority of the strains (68.9%) were isolated from males (mean age of 37.97 years), 88.5% of c. neoformans and only 37.5% of c. gattii strains were from hiv patients. ura5 ...201323861989
lipolytic enzymes involved in the virulence of human pathogenic fungi.pathogenic microbes secrete various enzymes with lipolytic activities to facilitate their survival within the host. lipolytic enzymes include extracellular lipases and phospholipases, and several lines of evidence have suggested that these enzymes contribute to the virulence of pathogenic fungi. candida albicans and cryptococcus neoformans are the most commonly isolated human fungal pathogens, and several biochemical and molecular approaches have identified their extracellular lipolytic enzymes. ...201323874127
[genotyping of cryptococcus neoformans/cryptococcus gattii complex clinical isolates from hospital "dr. julio c. perrando", resistencia city (chaco, argentina)].cryptococcosis is a fungal infection caused by yeast species of cryptococcus genus, particularly cryptococcus neoformans/cryptococcus gattii species complex. the knowledge of the cryptococcosis casuistic in northeastern argentina is scarce and there is no information about the molecular types circulating in this area. the aim of this study was to genotyping c. neoformans/c. gattii complex clinical isolates obtained at hospital "dr. julio c. perrando", resistencia city (chaco, argentina), in orde ...201323876270
cryptococcus infection in a non-hiv patient: a case report.cryptococcal infections are fungal infections most commonly seen in immunocompromised patients. chronic high-dose steroid may precipitate such an immunocompromised state and thus create susceptibility to fungal infections. cryptococcus neoformans is a saprophyte usually found in soil contaminated with pigeon droppings. suspicion to diagnose begins with clinical symptoms that can be non-specific such as fevers, cough, and headaches. we present a case of steroid-induced cryptococcal infection in a ...201223882378
granulomatous rhinitis due to candida parapsilosis in a cat.a 9-year-old female spayed domestic medium hair cat presented to the referring veterinarian with a 2-week history of sneezing, which progressed to swelling over the nasal planum. the cat had been under veterinary care for inflammatory bowel disease and had been treated with 1.25 mg/kg prednisolone once a day for approximately 1 year. on physical examination, an approximately 2-3 mm diameter, round polypoid pink soft-tissue mass was protruding slightly from the right nostril. through histologic e ...201323883665
synthesis and antifungal activities of miltefosine analogs.miltefosine is an alkylphosphocholine that shows broad-spectrum in vitro antifungal activities and limited in vivo efficacy in mouse models of cryptococcosis. to further explore the potential of this class of compounds for the treatment of systemic mycoses, nine analogs (3a-3i) were synthesized by modifying the choline structural moiety and the alkyl chain length of miltefosine. in vitro testing of these compounds against the opportunistic fungal pathogens candida albicans, candida glabrata, can ...201323891181
il-33 signaling regulates innate and adaptive immunity to cryptococcus neoformans.susceptibility to progressive infection with the fungus cryptococcus neoformans is associated with an allergic pattern of lung inflammation, yet the factors that govern this host response are not clearly understood. using a clinically relevant mouse model of inhalational infection with virulent c. neoformans h99, we demonstrate a role for il-33-dependent signaling in host immune defense. infection of balb/c mice with 10(4) cfu of c. neoformans h99 caused a time-dependent induction of il-33 with ...201323894196
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
a high-throughput screening assay for fungicidal compounds against cryptococcus neoformans.cryptococcus neoformans is a pathogenic fungus that causes meningitis worldwide, particularly in human immunodeficiency virus (hiv)-infected individuals. although amphotericin b is the "gold standard" treatment for cryptococcal meningitis, the toxicity and inconvenience of intravenous injection emphasize a need for development of new anticryptocccal drugs. recent data from humans and animal studies suggested that a nutrient-deprived host environment may exist in cryptococcal meningitis. thus, a ...201423896686
methamphetamine enhances cryptococcus neoformans pulmonary infection and dissemination to the brain.methamphetamine (meth) is a major addictive drug of abuse in the united states and worldwide, and its use is linked to hiv acquisition. the encapsulated fungus cryptococcus neoformans is the most common cause of fungal meningitis in patients with aids. in addition to functioning as a central nervous system stimulant, meth has diverse effects on host immunity. using a systemic mouse model of infection and in vitro assays in order to critically assess the impact of meth on c. neoformans pathogenes ...201323900172
isolation of cryptococcus neoformans and other opportunistic fungi from pigeon droppings.invasive fungal infections cause considerable morbidity and mortality in immunocompromised hosts. pigeon droppings could especially be a potential carrier in the spread of pathogenic yeasts and mold fungi into the environment. the objective of this study was to isolation of cryptococcus neoformans and other opportunistic fungi from pigeon droppings.201323901339
donor-derived cryptococcus infection in liver transplant: case report and literature review.cryptococcosis occurring within 30 days after transplant is unusual. we present a case of cryptococcosis diagnosed within 2 weeks of liver transplant and cryptococcal infection transmitted by liver transplant is considered as the cause. a 63-year-old woman with hepatitis c virus-related cirrhosis and hepatocellular carcinoma had an orthotopic liver transplant from a 45-year-old donor. the immediate postoperative course was smooth, although she was confused with a fever, tachycardia, respiratory ...201423901902
new compounds, chemical composition, antifungal activity and cytotoxicity of the essential oil from myrtus nivellei batt. & trab., an endemic species of central sahara.myrtus nivellei batt. & trab. (myrtaceae) known as sahara myrtle is appreciated by the touaregs as medicinal plant. infusion of leaves is employed against diarrhea and blennorrhea. crushed leaves added to oil or to butter ointment have been traditionally used for the treatment of dermatosis. aim of the study is to consider the traditional medicinal uses and the lack of scientific studies on their biological activities, the present study was designed to elucidate the chemical composition, the ant ...201323911425
requirement and redundancy of the src family kinases fyn and lyn in perforin-dependent killing of cryptococcus neoformans by nk cells.natural killer (nk) cells directly recognize and kill fungi, such as the pathogenic fungus cryptococcus neoformans, via cytolytic mechanisms. however, the precise signaling pathways governing this nk cell microbicidal activity and the implications for fungal recognition are still unknown. previously, it was reported that nk cell anticryptococcal activity is mediated through a conserved phosphatidylinositol 3-kinase-extracellular signal-regulated kinase 1/2 (pi3k-erk1/2) pathway. using yt (a huma ...201323918783
identification of the galactosyltransferase of cryptococcus neoformans involved in the biosynthesis of basidiomycete-type glycosylinositolphosphoceramide.the pathogenic fungus cryptococcus neoformans synthesizes a complex family of glycosylinositolphosphoceramide (gipc) structures. these glycosphingolipids (gsls) consist of mannosylinositolphosphoceramide (mipc) extended by β1-6-linked galactose, a unique structure that has to date only been identified in basidiomycetes. further extension by up to five mannose residues and a branching xylose has been described. in this study, we identified and determined the gene structure of the enzyme ggt1, whi ...201323926231
iron acquisition in the human fungal pathogen cryptococcus neoformans.iron sequestration by the vertebrate host is considered an efficient defense mechanism against pathogenic microbes. however, this mechanism, so called nutritional immunity, is often overcome by the iron acquisition systems that have evolved in microbial pathogens. numerous studies have been carried out to identify the key components of these systems and to understand their underlying mechanisms, including recent investigations in the basidiomycete fungal pathogen cryptococcus neoformans. iron ac ...201323927895
gβ-like cpcb plays a crucial role for growth and development of aspergillus nidulans and aspergillus fumigatus.growth, development, virulence and secondary metabolism in fungi are governed by heterotrimeric g proteins (g proteins). a gβ-like protein called gib2 has been shown to function as an atypical gβ in gpa1-camp signaling in cryptococcus neoformans. we found that the previously reported cpcb (cross pathway control b) protein is the ortholog of gib2 in aspergillus nidulans and aspergillus fumigatus. in this report, we further characterize the roles of cpcb in governing growth, development and toxige ...201323936193
pulmonary and meningeal cryptococcosis after corticosteroid therapy for autoimmune hepatitis: coexistence of cryptococci within pulmonary cancer nodule.a case of autoimmune hepatitis complicated with pulmonary and meningeal cryptococcosis during long-term treatment with corticosteroid is reported. an 84-year-old woman who received long-term corticosteroid therapy (40 mg/day prednisolone for two years) for autoimmune hepatitis developed a headache, slight fever, and anorexia and was diagnosed with cryptococcal meningitis two months prior to hospital admission. due to deterioration of her condition, the patient was transferred to our university h ...201323936710
antifungal cyclic peptides from the marine sponge microscleroderma herdmani.screening natural product extracts from the national cancer institute open repository for antifungal discovery afforded hits for bioassay-guided fractionation. using lc-ms analysis to generate chemical structure information on potentially active compounds, two new cyclic hexapeptides, microsclerodermins j (1) and k (2), were isolated from the deep-water sponge microscleroderma herdmani, along with microsclerodermins a (3) and b (4), previously isolated from an unidentified microscleroderma speci ...201223936761
kannurin, a novel lipopeptide from bacillus cereus strain ak1: isolation, structural evaluation and antifungal activities.this study was performed to isolate and characterize novel antifungal lipopeptide from bacillus cereus.201323937170
cryptococcus neoformans meningoencephalitis in a patient with idiopathic cd4+ t lymphocytopenia.cryptococcus neoformans is a leading cause of invasive cryptoccocal infections which include meningitis/meningoencephalitis, cerebral cryptococcoma, invasive pulmonary and mediastinal infection. invasive infection is mainly diagnosed in immunocompromised patients, especially in hiv-infected individuals. there is a rising number of patients with invasive cryptococcal infections in immunocompromised patients who are hiv-negative. among several primary immunodeficiency syndromes, considered as poss ...201323941014
isolated hepatobiliary cryptococcosis manifesting as obstructive jaundice in an immunocompetent child: case report and review of the literature.the majority of patients with symptomatic cryptococcosis have an underlying immunocompromising condition. in the absence of coexisting immunocompromising condition, cryptococcus neoformans is rarely considered in the differential diagnosis of obstructive jaundice that occurs in children with hilar masslike lesion. here, we report a 5-year-old boy without immunoglobulin or lymphocyte abnormalities who developed a hepatobiliary infection with c. neoformans. ultrasonography and computed tomography ...201423942746
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
cryptococcus neoformans ex vivo capsule size is associated with intracranial pressure and host immune response in hiv-associated cryptococcal meningitis.the cryptococcus neoformans polysaccharide capsule is a well-characterized virulence factor with immunomodulatory properties. the organism and/or shed capsule is postulated to raise intracranial pressure (icp) in cryptococcal meningitis (cm) by mechanical obstruction of cerebrospinal fluid (csf) outflow. little is known regarding capsule phenotype in human cryptococcosis. we investigated the relationship of ex vivo csf capsular phenotype with icp and csf immune response, as well as in vitro phen ...201423945372
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
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
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
functional characterization of camp-regulated gene, car1, in cryptococcus neoformans.the cyclic amp (camp) pathway plays a major role in growth, sexual differentiation, and virulence factor synthesis of pathogenic fungi. in cryptococcus neoformans, perturbation of the camp pathway, such as a deletion in the gene encoding adenylyl cyclase (cac1), causes defects in the production of virulence factors, including capsule and melanin production, as well as mating. previously, we performed a comparative transcriptome analysis of the ras- and camp-pathway mutants, which revealed 163 po ...201023956621
identification and functional characterization of a cryptococcus neoformans upc2 homolog.azoles are currently the most widely used class of antifungal drugs clinically, and are effective for treating fungal infections. target site of azoles is ergosterol biosynthesis in fungal cell membrane, which is absent in the mammalian host. however, the development of resistance to azole treatments in the fungal pathogen has become a significant challenge. here, we report the identification and functional characterization of a upc2 homolog in the human pathogen cryptococcus neoformans. upc2 pl ...201023956658
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
genetic circuits that govern bisexual and unisexual reproduction in cryptococcus neoformans.cryptococcus neoformans is a human fungal pathogen with a defined sexual cycle. nutrient-limiting conditions and pheromones induce a dimorphic transition from unicellular yeast to multicellular hyphae and the production of infectious spores. sexual reproduction involves cells of either opposite (bisexual) or one (unisexual) mating type. bisexual and unisexual reproduction are governed by shared components of the conserved pheromone-sensing cpk1 mapk signal transduction cascade and by mat2, the m ...201323966871
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
antimicrobial potential of endophytic fungi derived from three seagrass species: cymodocea serrulata, halophila ovalis and thalassia hemprichii.endophytic fungi from three commonly found seagrasses in southern thailand were explored for their ability to produce antimicrobial metabolites. one hundred and sixty endophytic fungi derived from cymodoceaserrulata (family cymodoceaceae), halophilaovalis and thalassiahemprichii (family hydrocharitaceae) were screened for production of antimicrobial compounds by a colorimetric broth microdilution test against ten human pathogenic microorganisms including staphylococcus aureus atcc 25923, a clini ...201323977310
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
cyclic dipeptides from rhabditid entomopathogenic nematode-associated bacillus cereus have antimicrobial activities.the cell free culture filtrate of bacillus cereus associated with an entomopathogenic nematode, rhabditis (oscheius) sp. exhibited strong antimicrobial activity. the ethyl acetate extract of the bacterial culture filtrate was purified by silica gel column chromatography to obtain four bioactive compounds. the structure and absolute stereochemistry of these compounds were determined based on extensive spectroscopic analyses (fabms, (1)h nmr, (13)c nmr, (1)h-(1)h cosy, (1)h-(13)c hmbc) and marfey' ...201423979826
cryptococcosis as an emerging systemic mycosis in dogs.to review the etiology, pathogenesis, and clinical presentations of canine cryptococcosis that are of relevance to veterinary emergency and critical care veterinarians. diagnosis, treatment, and public health considerations of the disease will also be discussed.201423981166
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
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