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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
[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
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
[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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
cryptococcal encephalopathy without persisting cerebrospinal fluid pleocytosis, a diagnostic challenge: case report and review of the literature. 201323756084
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
the crz1/sp1-like gene links survival under limited aeration, cell integrity and biofilm formation in the pathogenic yeast cryptococcus neoformans.limited aeration has been demonstrated to cause slowdown in proliferation and delayed budding, resulting eventually in a unique unbudded g2-arrest in the obligate aerobic pathogenic yeast cryptococcus neoformans. also, the ability to adapt to decreased oxygen levels during pathogenesis has been identified as a virulence factor in c. neoformans. the aim of this study was to identify and characterize genes that are necessary for the proliferation slowdown and g2-arrest caused by limited aeration.201423640031
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
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
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
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
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
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
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
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
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
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
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
spontaneous fungal peritonitis: a severe complication in patients with advanced liver cirrhosis.treatment of cirrhotic patients with spontaneous peritonitis using antibiotics occasionally fails. fungal infections may be one of the causes of antibiotic treatment failure in such patients. in this study we evaluated the clinical significance and characteristics of spontaneous fungal peritonitis (sfp). consecutive cirrhotic patients with spontaneous peritonitis treated between 2000 and 2005 at a tertiary care center in seoul, korea, were included. we analyzed the clinical characteristics and t ...201423996048
the intracellular life of cryptococcus neoformans.cryptococcus neoformans is a fungal pathogen with worldwide distribution. serological studies of human populations show a high prevalence of human infection, which rarely progresses to disease in immunocompetent hosts. however, decreased host immunity places individuals at high risk for cryptococcal disease. the disease can result from acute infection or reactivation of latent infection, in which yeasts within granulomas and host macrophages emerge to cause disease. in this review, we summarize ...201424050625
insights on the genotype distribution among cryptococcus neoformans and c. gattii portuguese clinical isolates.this study provides a comprehensive picture of the c. neoformans/c. gattii molecular types most often associated with human cryptococcosis in portugal and assesses the impact of c. gattii in these infections. one hundred and twenty-two clinical isolates, from distinct patients, were identified as c. neoformans and genotyped by ura5-rflp, with the molecular types vni (45.5 %) and vniii (30.9 %) being the most commonly found ones. the molecular types vnii (11.4 %) and vniv (11.4 %) were less abund ...201424077953
symptomatic relapse of hiv-associated cryptococcal meningitis: recurrent cryptococcal meningitis or cryptococcus-related immune reconstitution inflammatory syndrome?cryptococcosis, a significant opportunistic infection, has become a global concern since the advent of immunosuppressive chemotherapy or in immunodeficient patients. host responses range from a harmless colonization to disseminated disease. an accurate or definitive diagnosis in patients with cryptococcal meningitis is often delayed because of the similar clinical presentation and biochemical or cerebrospinal fluid findings to those of a variety of infectious and non-infectious aetiologies, most ...201424108453
fungal alternative splicing is associated with multicellular complexity and virulence: a genome-wide multi-species study.alternative splicing (as) is a cellular process that increases a cell's coding capacity from a limited set of genes. although as is common in higher plants and animals, its prevalence in other eukaryotes is mostly unknown. in fungi the involvement of as in gene expression and its effect on multi-cellularity and virulence is of great medical and economic interest. we present a genome-wide comparative study of as in 23 informative fungi of different taxa, based on alignments of public transcript s ...201424122896
simultaneous coinfection with cryptococcus neoformans and mycobacterium tuberculosis in an adult. 201424149279
unsplicer: mapping spliced rna-seq reads in compact genomes and filtering noisy splicing.accurate mapping of spliced rna-seq reads to genomic dna has been known as a challenging problem. despite significant efforts invested in developing efficient algorithms, with the human genome as a primary focus, the best solution is still not known. a recently introduced tool, truesight, has demonstrated better performance compared with earlier developed algorithms such as tophat and mapsplice. to improve detection of splice junctions, truesight uses information on statistical patterns of nucle ...201424259430
the er stress response and host temperature adaptation in the human fungal pathogen cryptococcus neoformans.in all eukaryotic cells, the er stress response is pivotal to survival and adaptation under stress conditions. during temperature adaptation in the human fungal pathogen cryptococcus neoformans, er stress is engaged transiently. studies of this response have demonstrated that both the engagement (turning on the response), as well as the resolution (turning off the response) are required for temperature adaptation and, therefore, pathogenesis. in this review, we synthesize our current understandi ...201424253500
the acid-catalysed synthesis of 7-azaindoles from 3-alkynyl-2-aminopyridines and their antimicrobial activity.the synthesis of 7-azaindoles from 3-alkynyl-2-aminopyridines using acidic conditions, namely, a mixture of trifluoroacetic acid (tfa) and trifluoroacetic anhydride (tfaa), is described. this methodology resulted in the synthesis of fifteen 7-azaindoles, with most containing substituents at the 2- and 5-positions. the majority of these were tested for antimicrobial activity against a range of bacteria and yeasts. the 7-azaindoles displayed the best activity against the yeasts, particularly again ...201424225656
synthetically modified l-histidine-rich peptidomimetics exhibit potent activity against cryptococcus neoformans.we describe the synthesis and antimicrobial evaluation of structurally new peptidomimetics, rich in synthetically modified l-histidine. two series of tripeptidomimetics were synthesized by varying lipophilicity at the c-2 position of l-histidine and at the n- and c-terminus. the data indicates that peptides (5f, 6f, 9f and 10f) possessing highly lipophilic adamantan-1-yl group displayed strong inhibition of cryptococcus neoformans. peptide 6f is the most potent of all with ic50 and mfc values of ...201424878194
effect of stereochemistry, chain length and sequence pattern on antimicrobial properties of short synthetic β-sheet forming peptide amphiphiles.in the face of mounting global antibiotics resistance, the identification and development of membrane-active antimicrobial peptides (amps) as an alternative class of antimicrobial agent have gained significant attention. the physical perturbation and disruption of microbial membranes by the amps have been proposed to be an effective means to overcome conventional mechanisms of drug resistance. recently, we have reported the design of a series of short synthetic β-sheet folding peptide amphiphile ...201424211081
[cryptococcal infection and sarcoidosis: a coincidence?].we report a case of cryptococcal infection that underwent in a patient with a medical history of asymptomatic sarcoidosis. this finding seems to be not incidental.201424210157
role of the apt1 protein in polysaccharide secretion by cryptococcus neoformans.flippases are key regulators of membrane asymmetry and secretory mechanisms. vesicular polysaccharide secretion is essential for the pathogenic mechanisms of cryptococcus neoformans. on the basis of the observations that flippases are required for polysaccharide secretion in plants and the putative apt1 flippase is required for cryptococcal virulence, we analyzed the role of this enzyme in polysaccharide release by c. neoformans, using a previously characterized apt1δ mutant. mutant and wild-typ ...201424337112
interleukin-17a enhances host defense against cryptococcal lung infection through effects mediated by leukocyte recruitment, activation, and gamma interferon production.infection of c57bl/6 mice with the moderately virulent cryptococcus neoformans strain 52d models the complex adaptive immune response observed in hiv-negative patients with persistent fungal lung infections. in this model, th1 and th2 responses evolve over time, yet the contribution of interleukin-17a (il-17a) to antifungal host defense is unknown. in this study, we show that fungal lung infection promoted an increase in th17 t cells that persisted to 8 weeks postinfection. our comparison of fun ...201424324191
the cryptococcus neoformans rim101 transcription factor directly regulates genes required for adaptation to the host.the rim101 protein is a conserved ph-responsive transcription factor that mediates important interactions between several fungal pathogens and the infected host. in the human fungal pathogen cryptococcus neoformans, the rim101 protein retains conserved functions to allow the microorganism to respond to changes in ph and other host stresses. this coordinated cellular response enables this fungus to effectively evade the host immune response. preliminary studies suggest that this conserved transcr ...201424324006
determinants of mortality in a combined cohort of 501 patients with hiv-associated cryptococcal meningitis: implications for improving outcomes.cryptococcal meningitis (cm) is a leading cause of death in individuals infected with human immunodeficiency virus (hiv). identifying factors associated with mortality informs strategies to improve outcomes.201424319084
full characterization of the cu-, zn-, and cd-binding properties of cnmt1 and cnmt2, two metallothioneins of the pathogenic fungus cryptococcus neoformans acting as virulence factors.we report here the full characterization of the metal binding abilities of cnmt1 and cnmt2, two cryptococcus neoformans proteins recently identified as metallothioneins (mts), which have been shown to play a crucial role in the virulence and pathogenicity of this human-infecting fungus. in this work, we first performed a thorough in silico study of the cnmt1 and cnmt2 genes, cdnas and corresponding encoded products. subsequently, the zn(ii)-, cd(ii)- and cu(i) binding abilities of both proteins ...201424317230
artemisinins: pharmacological actions beyond anti-malarial.artemisinins are a family of sesquiterpene trioxane lactone anti-malarial agents originally derived from artemisia annua l. the anti-malarial action of artemisinins involves the formation of free radicals via cleavage of the endoperoxide bond in its structure, which mediate eradication of the plasmodium species. with its established safety record in millions of malarial patients, artemisinins are also being investigated in diseases like infections, cancers and inflammation. artemisinins have bee ...201424316259
increased permeability of blood-brain barrier is mediated by serine protease during cryptococcus meningitis.to determine the role of serine protease in the disruption of the blood-brain barrier (bbb) during cryptococcus neoformans meningitis.201424398759
fungal central nervous system infections: prevalence and diagnosis.fungal infections of the central nervous system (cns) are rare but they pose a significant challenge. their prevalence spans a wide array of hosts including immunosuppressed and immunocompetent individuals, patients undergoing neurosurgical procedures and those carrying implantable cns devices. cryptococcus neoformans and aspergillus spp. remain the most common pathogens. magnetic resonance imaging can help localize the lesions, but diagnosis is challenging since invasive procedures may be neede ...201424392732
cryptococcus neoformans: historical curiosity to modern pathogen.the importance of the basidiomycete cryptococcus neoformans to human health has stimulated its development as an experimental model for both basic physiology and pathogenesis. we briefly review the history of this fascinating and versatile fungus, some notable aspects of its biology that contribute to virulence, and current tools available for its study.201424375706
interaction of surface molecules on cryptococcus neoformans with plasminogen.microbial pathogens are known to express molecules that interact with host proteins, leading to invasion and colonization. for example, some pathogenic microorganisms express proteins that bind to and enhance the activity of plasminogen. in this way, pathogens utilize the host fibrinolytic system to promote invasion. we found that triosephosphate isomerase (tpi), a glycolytic enzyme produced by staphylococcus aureus, bound to mannooligosaccharides from the pathogenic capsulated fungus cryptococc ...201424373348
rapidly progressive pneumonia caused by cryptococcus neoformans in the patient of granulomatosis with polyangiitis.a 57-year-old male who had been treated for granulomatosis with polyangiitis (gpa) presented with cough and back pain that had persisted for three days. mild infiltration shadows and nodules were found on computed tomography images at that time. increase of gpa lesions and/or bacterial pneumonia was initially suspected. however, serum cryptococcus neoformans antigen was positive and the chest x-ray findings had worsened by the following day despite of appropriate antibiotic treatment. thus, pneu ...201426029550
antifungal activity against cryptococcus neoformans strains and genotoxicity assessment in human leukocyte cells of euphorbia tirucalli l.in the last times, focus on plant research has increased all over the world. euphorbia tirucalli l., a plant known popularly as aveloz, and originally used in africa, has been drawing attention for its use in the united states and latin america, both for use as an ornamental plant and as a medicinal plant. e. tirucalli l. is a member of the family euphorbiaceae and contains many diterpenoids and triterpenoids, in particular phorbol esters, apparently the main constituent of this plant, which are ...201425763040
[cryptococcal meningitis in patients with diabetes and aids].cryptococcal meningitis is a severe aids-related infectious disease, with a high mortality rate. diabetes mellitus (dm) is a metabolic disorder very common worldwide. infectious diseases in diabetic patients are always more severe than in non-diabetic ones. the aim of this study was to compare the outcome of a group of hiv-positive patients with dm and cryptococcal meningitis with a similar group hiv-positive patients with cryptococcal meningitis, but without dm.201424365474
estrogen receptor antagonists are anti-cryptococcal agents that directly bind ef hand proteins and synergize with fluconazole in vivo.cryptococcosis is an infectious disease of global significance for which new therapies are needed. repurposing previously developed drugs for new indications can expedite the translation of new therapies from bench to beside. here, we characterized the anti-cryptococcal activity and antifungal mechanism of estrogen receptor antagonists related to the breast cancer drugs tamoxifen and toremifene. tamoxifen and toremifene are fungicidal and synergize with fluconazole and amphotericin b in vitro. i ...201424520056
the unfolded protein response (upr) pathway in cryptococcus.unique and evolutionarily conserved signaling pathways allow an organism to sense, respond to, and adapt to internal and external environmental cues at its biological niche. in eukaryotic cells, the unfolded protein response (upr) pathway regulates endoplasmic reticulum (er) homeostasis upon exposure to environmental changes causing er stress. the upr pathway of cryptococcus neoformans, an opportunistic fungal pathogen, which causes life-threatening meningoencephalitis in immunocompromised indiv ...201424504058
[cryptococcus neoformans var. gattii meningoencephalitis with cryptococcoma in an immunocompetent patient successfully treated by surgical resection].cryptococcosis is a fungal infection, which mainly invades the lungs and central nervous system. in japan, most cases of cryptococcosis are caused by cryptococcus neoformans(c. neoformans). until now, only three cases which the infectious agent was cryptococcus neoformans var. gattii(c. gattii)have been reported. as compared with cryptococcosis caused by c. neoformans, which is often observed in immunocompromised hosts, cryptococcosis caused by c. gattii occurs predominantly in immunocompetent h ...201424501185
visualizing non-lytic exocytosis of cryptococcus neoformans from macrophages using digital light microscopy.many aspects of the infection of macrophages by cryptococcus neoformans have been extensively studied and well defined. however, one particular interaction that is not clearly understood is non-lytic exocytosis. in this process, yeast cells are released into the extracellular space by a poorly understood mechanism that leaves both the macrophage and cn viable. here, we describe how to follow a large number of individually infected macrophages for a 24 hr infection period by time-lapsed microscop ...201425350860
unisexual reproduction of cryptococcus gattii.cryptococcus gattii is a basidiomycetous human fungal pathogen that typically causes infection in tropical and subtropical regions and is responsible for an ongoing outbreak in immunocompetent individuals on vancouver island and in the pacific northwest of the us. pathogenesis of this species may be linked to its sexual cycle that generates infectious propagules called basidiospores. a marked predominance of only one mating type (α) in clinical and environmental isolates suggests that a-α opposi ...201425337713
primary cutaneous cryptococcus neoformans serotype d presenting as painful ulcer and nodules on elbow of an immunocompetent patient. 201425261322
the cryptococcus neoformans transcriptome at the site of human meningitis.cryptococcus neoformans is the leading cause of fungal meningitis worldwide. previous studies have characterized the cryptococcal transcriptome under various stress conditions, but a comprehensive profile of the c. neoformans transcriptome in the human host has not been attempted. here, we extracted rna from yeast cells taken directly from the cerebrospinal fluid (csf) of two aids patients with cryptococcal meningitis prior to antifungal therapy. the patients were infected with strains of c. neo ...201424496797
proteogenomic analysis of pathogenic yeast cryptococcus neoformans using high resolution mass spectrometry.cryptococcus neoformans, a basidiomycetous fungus of universal occurrence, is a significant opportunistic human pathogen causing meningitis. owing to an increase in the number of immunosuppressed individuals along with emergence of drug-resistant strains, c. neoformans is gaining importance as a pathogen. although, whole genome sequencing of three varieties of c. neoformans has been completed recently, no global proteomic studies have yet been reported.201424484775
nigrosphaerin a a new isochromene derivative from the endophytic fungus nigrospora sphaerica.nigrosphaerin a, a new isochromene derivative (1), was isolated from the endophytic fungus nigrospora sphaerica and chemically identified as 3-(3,4-dihydroxyphenyl)-4,6,8-trihydroxy-1h-isochromen-1-one-6-o-β-d-glucopyranoside. in addition nineteen known compounds (2-20) were isolated from the same fungus and chemically identified. compounds (1-3, 5, and 7-16) were isolated for the first time from this fungus. in vitro antileukemic, antileishmanial, antifungal, antibacterial and antimalarial acti ...201427708743
a multiplex real-time pcr assay for identification of pneumocystis jirovecii, histoplasma capsulatum, and cryptococcus neoformans/cryptococcus gattii in samples from aids patients with opportunistic pneumonia.a molecular diagnostic technique based on real-time pcr was developed for the simultaneous detection of three of the most frequent causative agents of fungal opportunistic pneumonia in aids patients: pneumocystis jirovecii, histoplasma capsulatum, and cryptococcus neoformans/cryptococcus gattii. this technique was tested in cultured strains and in clinical samples from hiv-positive patients. the methodology used involved species-specific molecular beacon probes targeted to the internal transcrib ...201424478409
role of ferric reductases in iron acquisition and virulence in the fungal pathogen cryptococcus neoformans.iron acquisition is critical for the ability of the pathogenic yeast cryptococcus neoformans to cause disease in vertebrate hosts. in particular, iron overload exacerbates cryptococcal disease in an animal model, defects in iron acquisition attenuate virulence, and iron availability influences the expression of major virulence factors. c. neoformans acquires iron by multiple mechanisms, including a ferroxidase-permease high-affinity system, siderophore uptake, and utilization of both heme and tr ...201424478097
impact of surfactant protein d, interleukin-5, and eosinophilia on cryptococcosis.cryptococcus neoformans is an opportunistic fungal pathogen that initiates infection following inhalation. as a result, the pulmonary immune response provides a first line of defense against c. neoformans. surfactant protein d (sp-d) is an important regulator of pulmonary immune responses and is typically host protective against bacterial and viral respiratory infections. however, sp-d is not protective against c. neoformans. this is evidenced by previous work from our laboratory demonstrating t ...201424478083
fbp1-mediated ubiquitin-proteasome pathway controls cryptococcus neoformans virulence by regulating fungal intracellular growth in macrophages.cryptococcus neoformans is a human fungal pathogen that often causes lung and brain infections in immunocompromised patients, with a high fatality rate. our previous results showed that an f-box protein, fbp1, is essential for cryptococcus virulence independent of the classical virulence factors, suggesting a novel virulence control mechanism. in this study, we show that fbp1 is part of the ubiquitin-proteasome system, and we further investigated the mechanism of fbp1 function during infection. ...201424478071
il-4 receptor-alpha-dependent control of cryptococcus neoformans in the early phase of pulmonary infection.cryptococcus neoformans is an opportunistic fungal pathogen that causes lung inflammation and meningoencephalitis in immunocompromised people. previously we showed that mice succumb to intranasal infection by induction of pulmonary interleukin (il)-4rα-dependent type 2 immune responses, whereas il-12-dependent type 1 responses confer resistance. in the experiments presented here, il-4rα⁻/⁻ mice unexpectedly show decreased fungal control early upon infection with c. neoformans, whereas wild-type ...201424475277
defect of card9 leads to impaired accumulation of gamma interferon-producing memory phenotype t cells in lungs and increased susceptibility to pulmonary infection with cryptococcus neoformans.caspase recruitment domain-containing protein 9 (card9) is an adaptor molecule signal that is critical for nf-κb activation and is triggered through c-type lectin receptors (clrs), which are pattern recognition receptors that recognize carbohydrate structures. previous studies have reported that cryptococcus neoformans, a fungal pathogen that causes meningoencephalitis in aids patients, is recognized through some clrs, such as mannose receptors or dc-sign. however, the role of card9 in the host ...201424470469
proteomic profile of cryptococcus neoformans biofilm reveals changes in metabolic processes.cryptococcus neoformans, a pathogenic yeast, causes meningoencephalitis, especially in immunocompromised patients, leading in some cases to death. microbes in biofilms can cause persistent infections, which are harder to treat. cryptococcal biofilms are becoming common due to the growing use of brain valves and other medical devices. using shotgun proteomics we determine the differences in protein abundance between biofilm and planktonic cells. applying bioinformatic tools, we also evaluated the ...201424467693
mathematical modeling predicts enhanced growth of x-ray irradiated pigmented fungi.ionizing radiation is known for its cytotoxic and mutagenic properties. however, recent evidence suggests that chronic sub-lethal irradiation stimulates the growth of melanin-pigmented (melanized) fungi, supporting the hypothesis that interactions between melanin and ionizing photons generate energy useful for fungal growth, and/or regulate growth-promoting genes. there are no quantitative models of how fungal proliferation is affected by ionizing photon energy, dose rate, and presence versus ab ...201424454887
molecular epidemiology and antifungal susceptibility of serbian cryptococcus neoformans isolates.molecular typing and antifungal susceptibility testing of 34 clinical serbian cryptococcus neoformans isolates from 25 patients was retrospectively performed. amplified fragment length polymorphism (aflp) fingerprinting was used for genotyping, whereas a novel real-time pcr was used to determine the mating- and serotype. the antifungals amphotericin b, 5-fluorocytosine, fluconazole, voriconazole, itraconazole and posaconazole were used to determine the antifungal susceptibility profiles. the maj ...201424438323
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