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identification of a major ip5 kinase in cryptococcus neoformans confirms that pp-ip5/ip7, not ip6, is essential for virulence.fungal inositol polyphosphate (ip) kinases catalyse phosphorylation of ip3 to inositol pyrophosphate, pp-ip5/ip7, which is essential for virulence of cryptococcus neoformans. cryptococcal kcs1 converts ip6 to pp-ip5/ip7, but the kinase converting ip5 to ip6 is unknown. deletion of a putative ip5 kinase-encoding gene (ipk1) alone (ipk1δ), and in combination with kcs1 (ipk1δkcs1δ), profoundly reduced virulence in mice. however, deletion of kcs1 and ipk1 had a greater impact on virulence attenuatio ...201627033523
leveraging a high resolution microfluidic assay reveals insights into pathogenic fungal spore germination.germination of spores into actively growing cells is a process essential for survival and pathogenesis of many microbes. molecular mechanisms governing germination, however, are poorly understood in part because few tools exist for evaluating and interrogating the process. here, we introduce an assay that leverages developments in microfluidic technology and image processing to quantitatively measure germination with unprecedented resolution, assessing both individual cells and the population as ...201627026574
a rare cause of cerebral venous thrombosis: cryptococcal meningoencephalitis.cryptococcal meningoencephalitis (cm) is a serious central nervous system infection caused by cryptococcus neoformans, seen mostly in immunocompromised hosts and less in immunocompetent patients. the vast majority of cryptococcosis cases are seen as human immunodeficiency virus infections with advanced immunosuppression. meningitis and meningoencephalitis are the most common clinical manifestations. nevertheless, immunocompetent patients with cm are rarely reported. cerebral venous sinus thrombo ...201627025504
a case of pneumonia caused by pneumocystis jirovecii and cryptococcus neoformans in a patient with htlv-1 associated adult t- cell leukemia/lymphoma: occam's razor blunted.adult t-cell leukemia/lymphoma (atll) is usually preceded by infection with human t-cell lymphotropic virus i (htlv-i). patients with atll frequently get opportunistic infections of the lungs, intestines, and central nervous system. pneumocystis pneumonia is commonly known as an aids defining illness. grocott's methenamine silver stain of bronchoalveolar lavage (bal) samples obtained via bronchoscopy remain the gold standard for diagnosis. pulmonary cryptococcosis is seen in patients with t-cell ...201627024978
berberine antifungal activity in fluconazole-resistant pathogenic yeasts: action mechanism evaluated by flow cytometry and biofilm growth inhibition in candida spp.the incidence of fungal infections and, in particular, the incidence of fungal antibiotic resistance, which is associated with biofilm formation, have significantly increased, contributing to morbidity and mortality. thus, new therapeutic strategies need to be developed. in this context, natural products have emerged as a major source of possible antifungal agents. berberine is a protoberberine-type isoquinoline alkaloid isolated from the roots, rhizomes, and stem bark of natural herbs, such as ...201627021328
magnesium ion acts as a signal for capsule induction in cryptococcus neoformans.cryptococcal meningitis caused by cryptococcus neoformans, is a common opportunistic neural infection in immunocompromised individuals. cryptococcus meningitis is associated with fungal burden with larger capsule size in cerebrospinal fluid (csf). to understand the role of csf constituents in capsule enlargement, we have evaluated the effect of artificial csf on capsule induction in comparison with various other capsule inducing media. two different strains of c. neoformans, an environmental and ...201627014245
virulence of cryptococcus sp. biofilms in vitro and in vivo using galleria mellonella as an alternative model.cryptococcus neoformans and c. gattii are fungal pathogens that are most commonly found in infections of the central nervous system, which cause life-threatening meningoencephalitis and can grow as a biofilm. biofilms are structures conferring protection and resistance of microorganism to the antifungal drugs. this study compared the virulence of planktonic and biofilm cells of c. neoformans and c. gattii in galleria mellonella model, as well as, the quantification of gene transcripts lac1, ure1 ...201627014214
morphotype-specific effector functions of cryptococcus neoformans pum1.the basidiomycete fungal pathogen cryptococcus neoformans requires the puf protein, pum1, for hyphal morphogenesis during sexual development. in this study we found that pum1 was auto-repressive under growth as yeast, but that auto-repression was relieved during filamentous growth through utilization of an alternative transcription start site driven by the master filamentation regulator znf2. in addition, pum1 was required to stabilize the znf2 mrna through an indirect mechanism suggesting that ...201627008977
molecular typing of environmental cryptococcus neoformans/c. gattii species complex isolates from manaus, amazonas, brazil.cryptococcus neoformans and cryptococcus gattii are the main causative agents of cryptococcosis, a systemic fungal disease that affects internal organs and skin, and which is acquired by inhalation of spores or encapsulated yeasts. it is currently known that the c. neoformans/c. gattii species complex has a worldwide distribution, however, some molecular types seem to prevail in certain regions. few environmental studies of cryptococcus have been conducted in the brazilian amazon. this is the fi ...201627005969
cryptococcal therapies and drug targets: the old, the new and the promising.half a century after the introduction of amphotericin b the management of cryptococcosis remains unsatisfactory. the disease, caused primarily by the two fungal species cryptococcus neoformans and cryptococcus gattii, remains responsible for considerable morbidity and mortality despite standard medical care. current therapeutic options are limited to amphotericin b, azoles and 5-flucytosine. however, this organism has numerous well-characterized virulence mechanisms that are amenable to pharmaco ...201626990050
immune reconstitution syndrome in a human immunodeficiency virus infected child due to giardiasis leading to shock.human immunodeficiency virus (hiv)-associated immune reconstitution inflammatory syndrome has been reported in association with tuberculosis, herpes zoster (shingles), cryptococcus neoformans, kaposi's sarcoma, pneumocystis pneumonia, hepatitis b virus, hepatitis c virus, herpes simplex virus, histoplasma capsulatum, human papillomavirus, and cytomegalovirus. however, it has never been documented with giardiasis. we present a 7-year-old hiv infected girl who developed diarrhea and shock followin ...201726985424
[cryptococcal meningoencephalitis. epidemiology and mortality risk factors in pre- and post-haart era].cryptococcal meningoencephalitis (cm) is an uncommon entity, but remains a major cause of morbidity and mortality in patients with aids.201626971986
[multiple facial nodules revealing disseminated cryptococcosis in an immunocompetent patient].cryptococcosis is a potentially severe infection that usually occurs in a setting of immunosuppression. its occurrence outside of this context is rare. we report a case of disseminated cryptococcosis revealed by a spectacular skin disease in an immunocompetent patient.201626971369
cryptococcal osteomyelitis: a report of 5 cases and a review of the recent literature.cryptococcus neoformans is a fungal pathogen associated with advanced hiv disease and other disorders associated with immune dysfunction. the pulmonary and the central nervous system are the most common manifestations of the disease. localised osteomyelitis as the sole manifestation of extrapulmonary disease is rare. herein, we present five cases of cryptococcus osteomyelitis as the only manifestation of extrapulmonary disease. we also identified 84 additional cases of isolated cryptococcal oste ...201626968335
correction: iron regulation of the major virulence factors in the aids-associated pathogen cryptococcus neoformans. 201626953732
bloodstream infections in hiv-infected patients.in the combined antiretroviral therapy era, hiv-infected patients remain a vulnerable population for the onset of bloodstream infections (bsi). worldwide, nontyphoid salmonellae, streptococcus pneumoniae, escherichia coli, staphylococcus aureus and coagulase negative staphylococci are the most important pathogens. intravenous catheter associated infection, skin-soft tissue infection and endocarditis are associated with gram-positive bacteremia. among the gram-negative, nontyphoidal salmonella ha ...201626950194
isolation, identification and molecular typing of cryptococcus neoformans from pigeon droppings and other environmental sources in tripoli, libya.cryptococcus neoformans and c. gattii are the major cause of fungal meningitis, a potentially lethal mycosis. since pigeon excreta and other environmental sources can be considered a significant environmental reservoir of this species in urban areas, 100 samples of pigeon excreta and 420 samples from eucalyptus camaldulensis and olea europaea (olive tree) around the city of tripoli, libya, were collected. c. neoformans was isolated and identified using standard biochemical assays from 46 samples ...201626943725
[mechanism of cryptococcus meningoencephalitis].cryptococcus neoformans and cryptococcus gattii are fungal pathogens that cause diseases in humans. cryptococcal species mainly enter the body by inhalation and in most cases are eliminated by host defense mechanisms. some cases, however, progress to pneumonia and subsequent dissemination of the infection to the central nervous system (cns), leading to meningoencephalitis. cryptococcus can cross the blood-brain barrier transcellularly, paracellularly and through infected phagocytes (the trojan h ...201626936349
cryptococcus neoformans infection in malignancy.cryptococcosis is an opportunistic invasive fungal infection that is well described and easily recognised when it occurs as meningitis in hiv-infected persons. malignancy and its treatment may also confer a higher risk of infection with cryptococcus neoformans, but this association has not been as well described. a case of cryptococcosis in a cancer patient is presented, and all cases of coincident c. neoformans infection and malignancy in adults published in the literature in english between 19 ...201626932366
severe cryptococcal-associated neurological immune reconstitution inflammatory syndrome in a renal transplant recipient treated with adalimumab.cryptococcosis is a major concern in organ transplant recipients. a decrease in immunosuppressants following the initiation of antifungal therapy is currently recommended, but can occasionally be complicated by the onset of immune reconstitution inflammatory syndrome (iris). we report on a case of cryptococcosis in a kidney transplant recipient, compounded by severe neurological iris, the outcome of which was unfavorable despite the use of anti-tumor necrosis factor-alpha monoclonal antibodies.201626929435
refractory and/or relapsing cryptococcosis associated with acquired immune deficiency syndrome: clinical features, genotype, and virulence factors of cryptococcus spp. isolates.refractory and relapsing crytocococcosis in acquired immune deficiency syndrome (aids) patients have a poor prognosis. the risk factors for this complicated infection course were evaluated by comparing refractory and/or relapsing cryptococcosis in human immunodeficiency virus-coinfected patients (cohort 1) with another group of aids patients who adequately responded to antifungals (cohort 2). except for one isolate of cryptococcus gattii from a cohort 2 case, all other isolates were identified a ...201626928832
cryptococcus neoformans: tripping on acid in the phagolysosome.cryptococcus neoformans (cn) is a basidiomycetous pathogenic yeast that is a frequent cause of meningoencephalitis in immunocompromised individuals. cn is a facultative intracellular pathogen in mammals, insects and amoeba. cn infection occurs after inhalation of spores or desiccated cells from the environment. after inhalation cn localizes to the lungs where it can be phagocytosed by alveolar macrophages. cn is surrounded by a polysaccharide capsule that helps the fungus survive in vivo by inte ...201626925039
cross-reactivity in cryptococcus antigen latex agglutination test in two commercial kits.this article presents an examination of the cross-reactivity of pathogenic fungi with cryptococcus neoformans in two commercial cryptococcus antigen latex agglutination tests performed across 39 fungal strains. some fungi were newly indicated as cryptococcus cross-reactive, and the two kits showed differences in cross-reactive fungi.201626922300
all about that fat: lipid modification of proteins in cryptococcus neoformans.lipid modification of proteins is a widespread, essential process whereby fatty acids, cholesterol, isoprenoids, phospholipids, or glycosylphospholipids are attached to polypeptides. these hydrophobic groups may affect protein structure, function, localization, and/or stability; as a consequence such modifications play critical regulatory roles in cellular systems. recent advances in chemical biology and proteomics have allowed the profiling of modified proteins, enabling dissection of the funct ...201626920881
innate host defenses against cryptococcus neoformans.cryptococcus neoformans, the predominant etiological agent of cryptococcosis, can cause life-threatening infections of the central nervous system in immunocompromised and immunocompetent individuals. cryptococcal meningoencephalitis is the most common disseminated fungal infection in aids patients, and remains the third most common invasive fungal infection among organ transplant recipients. the administration of highly active antiretroviral therapy (haart) has resulted in a decrease in the numb ...201626920880
impact of resistance to fluconazole on virulence and morphological aspects of cryptococcus neoformans and cryptococcus gattii isolates.cryptococcus sp. are responsible for around 1 million cases of meningitis every year. fluconazole (flu) is commonly used in the treatment of cryptococcosis, mainly in immunocompromised patients and the resistance is usually reported after long periods of treatment. in this study, the morphological characterization and virulence profile of flu-susceptible and flu-resistant clinical and environmental isolates of c. neoformans and c. gattii were performed both in vitro and in vivo using the galleri ...201626909069
enhanced virulence of histoplasma capsulatum through transfer and surface incorporation of glycans from cryptococcus neoformans during co-infection.cryptococcus neoformans (cn) and histoplasma capsulatum (hc) co-exist in the environment and occasionally co-infect individuals, which can lead to severe disease/lethal outcomes. we investigated specific interactions between cn-hc to determine the impact of synchronous infection in virulence and disease. co-infected mice had significantly higher mortality than infection with either species or acapsular cn-hc. coating of hc with cryptococcal glycans (cn-gly) resulted in higher pulmonary fungal bu ...201626908077
cryptococcus and phagocytes: complex interactions that influence disease outcome.cryptococcus neoformans and c. gattii are fungal pathogens that cause life-threatening disease. these fungi commonly enter their host via inhalation into the lungs where they encounter resident phagocytes, including macrophages and dendritic cells, whose response has a pronounced impact on the outcome of disease. cryptococcus has complex interactions with the resident and infiltrating innate immune cells that, ideally, result in destruction of the yeast. these phagocytic cells have pattern recog ...201626903984
usefulness of silkworm as a host animal for understanding pathogenicity of cryptococcus neoformans.we propose cryptococcus neoformans infection model using silkworm for understanding cryptococcosis and screening of therapeutically effective antibiotics. silkworm is an insect whose rearing methods were established through a long history of the sericulture industry. silkworm facilitates experiments using a large number of individuals because of low cost for rearing and few ethical problems caused by killing animals. silkworm can be reared at 37˚c to perform infection experiments at same tempera ...201626902902
cd44-mediated monocyte transmigration across cryptococcus neoformans-infected brain microvascular endothelial cells is enhanced by hiv-1 gp41-i90 ectodomain.cryptococcus neoformans (cn) is an important opportunistic pathogen in the immunocompromised people, including aids patients, which leads to fatal cryptococcal meningitis with high mortality rate. previous researches have shown that hiv-1 gp41-i90 ectodomain can enhance cn adhesion to and invasion of brain microvascular endothelial cell (bmec), which constitutes the blood brain barrier (bbb). however, little is known about the role of hiv-1 gp41-i90 in the monocyte transmigration across cn-infec ...201626897523
multiple opportunistic fungal infections in an individual with severe hiv disease: a case report.fungal infections have been commonly diagnosed in individuals with advanced hiv disease. cryptococcosis, pneumocystosis, and histoplasmosis are the most frequent systemic mycoses in people suffering from hiv/aids.201626896884
cryptococcus neoformans intracellular proliferation and capsule size determines early macrophage control of infection.cryptococcus neoformans is a significant fungal pathogen of immunocompromised patients. many questions remain regarding the function of macrophages in normal clearance of cryptococcal infection and the defects present in uncontrolled cryptococcosis. two current limitations are: 1) the difficulties in interpreting studies using isolated macrophages in the context of the progression of infection, and 2) the use of high resolution imaging in understanding immune cell behavior during animal infectio ...201626887656
eucalyptus tree: a potential source of cryptococcus neoformans in egyptian environment.in egypt, the river red gum (eucalyptus camaldulensis) is a well-known tree and is highly appreciated by the rural and urban dwellers. the role of eucalyptus trees in the ecology of cryptococcus neoformans is documented worldwide. the aim of this survey was to show the prevalence of c. neoformans during the flowering season of e. camaldulensis at the delta region in egypt. three hundred and eleven samples out of two hundred eucalyptus trees, including leaves, flowers, and woody trunks, were coll ...201626884765
cryptococcus neoformans thermotolerance to avian body temperature is sufficient for extracellular growth but not intracellular survival in macrophages.cryptococcus neoformans is a fatal fungal pathogen of humans that efficiently parasitises macrophages. birds can be colonised by cryptococci and can transmit cryptococcosis to humans via inhalation of inoculated bird excreta. however, colonisation of birds appears to occur in the absence of symptomatic infection. here, using a pure population of primary bird macrophages, we demonstrate a mechanism for this relationship. we find that bird macrophages are able to suppress the growth of cryptococci ...201626883088
the fungus tremella mesenterica encodes the longest metallothionein currently known: gene, protein and metal binding characterization.fungal cu-thioneins, and among them, the paradigmatic neurospora crassa metallothionein (mt) (26 residues), were once considered as the shortest mts--the ubiquitous, versatile metal-binding proteins--among all organisms, and thus representatives of their primeval forms. nowadays, fungal mts of diverse lengths and sequence features are known, following the huge heterogeneity of the kingdom of fungi. at the opposite end of n. crassa mt, the recently reported cryptococcus neoformans cnmt1 and cnmt2 ...201626882011
regulation of the fungal secretome.the ability of countless representatives of the kingdom fungi to adapt to and proliferate in diverse environments is facilitated by regulation of their secretomes to respond to changes in environmental conditions and to mediate interactions with other organisms. secretome changes often fulfill common functions of nutrient acquisition, facilitation of host/symbiont interactions, cell wall modification, and optimization of the enzyme suite to adapt to new environmental resources. in this review, w ...201626879194
ras-related c3 botulinum toxin substrate (rac) and src family kinases (sfk) are proximal and essential for phosphatidylinositol 3-kinase (pi3k) activation in natural killer (nk) cell-mediated direct cytotoxicity against cryptococcus neoformans.the activity of rac in leukocytes is essential for immunity. however, its role in nk cell-mediated anti-microbial signaling remains unclear. in this study, we investigated the role of rac in nk cell mediated anti-cryptococcal killing. we found thatcryptococcus neoformansindependently activates both rac and sfk pathways in nk cells, and unlike in tumor killing,cryptococcusinitiated a novel rac → pi3k → erk cytotoxicity cascade. remarkably, rac was not required for conjugate formation, despite its ...201626867574
susceptibility profile and epidemiological cut-off values of cryptococcus neoformans species complex from argentina.epidemiological cut-off values (ecvs) based on minimal inhibitory concentration (mic) distribution have been recently proposed for some antifungal drug/cryptococcus neoformans combinations. however, these ecvs vary according to the species studied, being serotypes and the geographical origin of strains, variables to be considered. the aims were to define the wild-type (wt) population of the c. neoformans species complex (c. neoformans) isolated from patients living in argentina, and to propose e ...201626865081
simultaneous detection of five pathogens from cerebrospinal fluid specimens using luminex technology.early diagnosis and treatment are crucial for the outcome of central nervous system (cns) infections. in this study, we developed a multiplex pcr-luminex assay for the simultaneous detection of five major pathogens, including mycobacterium tuberculosis, cryptococcus neoformans, streptococcus pneumoniae, and herpes simplex virus types 1 and 2, which frequently cause cns infections. through the hybridization reaction between multiplex pcr-amplified targets and oligonucleotide "anti-tag" sequences, ...201626861363
unveiling protein kinase a targets in cryptococcus neoformans capsule formation.the protein kinase a (pka) signal transduction pathway has been associated with pathogenesis in many fungal species. geddes and colleagues [mbio 7(1):e01862-15, 2016, doi:10.1128/mbio.01862-15] used quantitative proteomics approaches to define proteins with altered abundance during protein kinase a (pka) activation and repression in the opportunistic human fungal pathogen cryptococcus neoformans. they observed an association between microbial pka signaling and ubiquitin-proteasome regulation of ...201626861014
in vitro synergistic effects of chlorpromazine and sertraline in combination with amphotericin b against cryptococcus neoformans var. grubii.cryptococcus neoformans is encapsulated yeast that causes cryptococcosis. the cryptococcal meningitis may cause neuropsychiatric symptoms. here, we evaluated the in vitro activity of amphotericin b (amb), chlorpromazine (clor), and sertraline (sert) alone or in combination against clinical isolates of c. neoformans considering the capsular induction in vitro. susceptibility tests were carried out using the broth microdilution method in accordance with the clsi document m27-a3. the combination [c ...201626847460
thoracolumbar scoliosis due to cryptococcal osteomyelitis: a case report and review of the literature.cryptococcus neoformans causes opportunistic infections in immunocompromised patients, with vertebral osteomyelitis being a very rare involvement.this study is to present a case of thoracolumbar scoliosis occurring in the setting of cryptococcal osteomyelitis.pharmacological intervention with anticryptococcal medicine and medical management of immune hemolytic anemia were administered. after initial acute stabilization, she underwent spinal debridement and fusion on october 29, 2008. she eventua ...201626844472
[successful treatment for cryptococcal meningoencephalitis complicated by cerebral salt-wasting syndrome in a patient with chronic lymphocytic leukemia: a clinical case].cryptococcus neoformans is a common agent of fungal meningoencephalitis in immunocompromised patients. cerebral salt-wasting syndrome is one of the rare causes of severe hyponatremia in patients with cns diseases. the paper describes the first clinical case of a patient, whose onset of chronic lymphocytic leukemia was complicated by cryptococcal meningoencephalitis presenting with mental disorders and severe electrolytic imbalance. antifungal treatment with amphotericin b and fluconazole could a ...201526821425
high-throughput screen in cryptococcus neoformans identifies a novel molecular scaffold that inhibits cell wall integrity pathway signaling.cryptococcus neoformans is one of the most important human fungal pathogens; however, no new therapies have been developed in over 50 years. fungicidal activity is crucially important for an effective anticryptococal agent and, therefore, we screened 361,675 molecules against c. neoformans using an adenylate kinase release assay that specifically detects fungicidal activity. a set of secondary assays narrowed the set of hits to molecules that interfere with fungal cell wall integrity and identif ...201626807437
human immune response varies by the degree of relative cryptococcal antigen shedding.background.  cerebrospinal fluid (csf) cryptococcal glucuronoxylomannan antigen (crag) titers generally correlate with quantitative fungal culture burden; however, correlation is not precise. some patients have higher crag titers with lower fungal burdens and vice versa. we hypothesized that the relative discordancy between crag titer and quantitative culture burden reflects the relative degree of crag shedding by cryptococcus neoformans and is associated with human immune responses. methods.  o ...201626807426
the investigational fungal cyp51 inhibitor vt-1129 demonstrates potent in vitro activity against cryptococcus neoformans and cryptococcus gattii.thein vitroactivities of the novel fungal cyp51 inhibitor vt-1129 were evaluated against a large panel ofcryptococcus neoformansandcryptococcus gattiiisolates. vt-1129 demonstrated potent activities against bothcryptococcusspecies as demonstrated by low mic50and mic90values. forc. gattii, thein vitropotency was maintained against all genotypes. in addition, significantly lower geometric mean mics were observed for vt-1129 than for fluconazole againstc. neoformans, including isolates with reduced ...201626787697
structural analysis of glucosylceramides (glccer) from species of the pseudallescheria/scedosporium complex.glucosylceramides (glccer) are the main neutral glycosphingolipids expressed in fungal cells. in this work, glucosylceramides (glccer) were extracted from three strains of scedosporium (pseudallescheria) boydii, one strain of pseudallescheria ellipsoidea and one strain of pseudallescheria angusta and purified by several chromatographic steps. using high-performance thin layer chromatography (hptlc), we found a similarity between glccer obtained from all of the analysed strains. a detailed struct ...201626781373
evasion of innate immune responses by the highly virulent cryptococcus gattii by altering capsule glucuronoxylomannan structure.cryptococcus neoformans causes life-threatening diseases mainly in immunosuppressed hosts such as aids patients; c. gattii causes disseminated infections even in healthy hosts. to identify the possible molecular mechanisms underlying this difference in virulence, we investigated the survival and histopathology of lung tissue in wild-type and cd4-depleted mice infected with c. neoformans h99 and c. gattii jp02 (the highly virulent strain isolated in japan); we then compared dendritic cell (dc) cy ...201526779451
cryptococcal infection of the ventriculoperitoneal shunt in an immunocompetent patient.ventriculoperitoneal shunting is an effective treatment for hydrocephalus. ventriculoperitoneal shunt (vps) infection is a common complication. cryptococcus neoformans as an implicated organism is rare. in this report, we describe a patient with cryptococcal vps infection.201626778598
multilocus sequence typing analysis reveals that cryptococcus neoformans var. neoformans is a recombinant population.cryptococcus neoformans var. neoformans (serotype d) represents about 30% of the clinical isolates in europe and is present less frequently in the other continents. it is the prevalent etiological agent in primary cutaneous cryptococcosis as well as in cryptococcal skin lesions of disseminated cryptococcosis. very little is known about the genotypic diversity of this cryptococcus subtype. the aim of this study was to investigate the genotypic diversity among a set of clinical and environmental c ...201626768709
a glucuronoxylomannan-associated immune signature, characterized by monocyte deactivation and an increased interleukin 10 level, is a predictor of death in cryptococcal meningitis.cryptococcal meningitis remains a significant cause of death among human immunodeficiency virus type 1 (hiv)-infected persons in africa. we aimed to better understand the pathogenesis and identify immune correlates of mortality, particularly the role of monocyte activation.201626768248
interleukin-17 mediated differences in the pathogenesis of hiv-1-associated tuberculous and cryptococcal meningitis.mycobacterium tuberculosis and cryptococcus neoformans are major causes of meningitis in hiv-1-infected patients. identifying differences in the inflammatory profiles of hiv-1-associated tuberculous meningitis (tbm) and cryptococcal meningitis may inform differences in immunopathogenic mechanisms in these diseases. in this study we compared the clinical and inflammatory features of hiv-1-associated tbm, and cryptococcal meningitis.201626765934
halogenated benzoate derivatives of altholactone with improved anti-fungal activity.altholactone exhibited the anti-fungal activity with a high mic value of 128 μg ml(-1) against cryptococcus neoformans and saccharomyces cerevisiae. fifteen ester derivatives of altholactone 1-15 were modified by esterification and their structures were confirmed by spectroscopic methods. most of the ester derivatives exhibited stronger anti-fungal activities than that of the precursor altholactone. 3-bromo- and 2,4-dichlorobenzoates (7 and 15) exhibited the lowest minimal inhibitory concentrati ...201626765144
analysis of the protein kinase a-regulated proteome of cryptococcus neoformans identifies a role for the ubiquitin-proteasome pathway in capsule formation.the opportunistic fungal pathogen cryptococcus neoformans causes life-threatening meningitis in immunocompromised individuals. the expression of virulence factors, including capsule and melanin, is in part regulated by the cyclic-amp/protein kinase a (camp/pka) signal transduction pathway. in this study, we investigated the influence of pka on the composition of the intracellular proteome to obtain a comprehensive understanding of the regulation that underpins virulence. through quantitative pro ...201626758180
local gm-csf-dependent differentiation and activation of pulmonary dendritic cells and macrophages protect against progressive cryptococcal lung infection in mice.patients with acquired deficiency in gm-csf are susceptible to infections with cryptococcus neoformans and other opportunistic fungi. we previously showed that gm-csf protects against progressive fungal disease using a murine model of cryptococcal lung infection. to better understand the cellular and molecular mechanisms through which gm-csf enhances antifungal host defenses, we investigated temporal and spatial relationships between myeloid and lymphoid immune responses in wild-type c57bl/6 mic ...201626755822
primary larynx cryptococcus neoformans infection: a distinctive clinical entity.cryptococcus neoformans can directly infect the vocal cords. endoscopic findings were undistinctive from most infiltrative diseases. tissue biopsy was essential for the diagnosis. inhaled corticosteroids can predispose to the infection, and fluconazole 400 mg daily for at least 6 weeks appeared to be minimal to achieve a permanent cure.201526753169
from two to one: unipolar sexual reproduction.while sexual reproduction is universal in eukaryotes, and shares conserved core features, the specific aspects of sexual reproduction can differ dramatically from species to species. this is also true in fungi. among fungal species, mating determination can vary from tetrapolar with more than a thousand different mating types, to bipolar with only two opposite mating types, and finally to unipolar without the need of a compatible mating partner for sexual reproduction. cryptococcus neoformans is ...201526744600
antibacterial and antifungal screening of natural products sourced from australian fungi and characterisation of pestalactams d-f.eighteen natural products sourced from australian micro- or macro-fungi were screened for antibacterial and antifungal activity. this focused library was comprised of caprolactams, polyamines, quinones, and polyketides, with additional large-scale isolation studies undertaken in order to resupply previously identified compounds. chemical investigations of the re-fermented culture from the endophytic fungus pestalotiopsis sp. yielded three caprolactam analogues, pestalactams d-f, along with large ...201626743853
activity of sertraline against cryptococcus neoformans: in vitro and in vivo assays.cryptococcus neoformans infection is an important cause of meningitis in hiv/aids endemic regions. antifungals for its management include amphotericin b, flucytosine, and fluconazole. recently, treatment of this mycosis with sertraline has been studied with variable clinical outcomes. the aim of the study was to assess the in vitro antifungal effect of sertraline against clinical isolates of cryptococcus spp. as well as its in vivo activity in a murine model of cryptococcal meningoencephalitis. ...201626705833
protection against experimental cryptococcosis following vaccination with glucan particles containing cryptococcus alkaline extracts.a vaccine capable of protecting at-risk persons against infections due to cryptococcus neoformans and cryptococcus gattii could reduce the substantial global burden of human cryptococcosis. vaccine development has been hampered though, by lack of knowledge as to which antigens are immunoprotective and the need for an effective vaccine delivery system. we made alkaline extracts from mutant cryptococcal strains that lacked capsule or chitosan. the extracts were then packaged into glucan particles ...201526695631
antifungal susceptibility of clinical and environmental cryptococcus neoformans and cryptococcus gattii isolates in jabalpur, a city of madhya pradesh in central india.in this study, we present antifungal susceptibility data of clinical and environmental isolates of central indian cryptococcus neoformans (serotype a, n = 8 and n = 50 respectively) and cryptococcus gattii (serotype b, n = 01 and n = 04 respectively). susceptibilities to fluconazole, itraconazole and ketoconazole were determined by using nccls broth micro-dilution methodology. the total number of resistant strains for fluconazole in case of c. neoformans and c. gattii showed a significant differ ...201626691471
contrasted patterns in mating-type chromosomes in fungi: hotspots versus coldspots of recombination.it is striking that, while central to sexual reproduction, the genomic regions determining sex or mating-types are often characterized by suppressed recombination that leads to a decrease in the efficiency of selection, shelters genetic load, and inevitably contributes to their genic degeneration. research on model and lesser-explored fungi has revealed similarities in recombination suppression of the genomic regions involved in mating compatibility across eukaryotes, but fungi also provide oppo ...201526688691
cryptococcosis presenting as a colonic ulcer in a kidney transplant recipient: a case report.we present a case of a 59-year-old woman with chagas disease who received a kidney transplant. at month 44 post-transplantation, the patient presented with diarrhea that had persisted for 2 months. colonoscopy showed a colon ulcer and differential diagnoses included cytomegalovirus, bacteria, or parasite infection; drug-related diarrhea; crohn's disease; celiac disease; and malignancy. the ulcer tissue was positive for cryptococcus neoformans. successful treatment consisted of amphotericin b for ...201526680095
cryptococcus neoformans var. grubii infection in hiv-seronegative patients from northeast india: report of two cases with review of literature.cryptococcus neoformans infection can occur in a wide range of hosts ranging from those who are severely immunosuppressed to those who are apparently immunocompetent. two apparently immunocompetent hiv-seronegative patients with cryptococcal meningitis and multiple skin lesions, both due to c. neoformans var. grubii, are reported. pregnancy was found as an associated factor in cryptococcal meningitis in a 20-year-old female patient from arunachal pradesh. multiple skin lesions were the presentin ...201626677012
necrotizing fasciitis caused by cryptococcus gattii.necrotizing fasciitis (nf) is a severe soft-tissue infection that can lead to high morbidity and mortality. the etiology of nf is often polymicrobial. although rare, fungal organisms have been known to cause nf. cryptococcus is a fungal infection that may lead to nf. here we report the case of a 73-year-old man who had diabetes and presented with pain and swelling in the left hand after being bitten by an insect over the dorsum of the hand. operative débridement revealed nf caused by cryptococcu ...201526665255
comparison of biotyping methods as alternative identification tools to molecular typing of pathogenic cryptococcus species in sub-saharan africa.cryptococcal meningitis is the leading fungal infection and aids defining opportunistic illness in patients with late stage hiv infection, particularly in south-east asia and sub-saharan africa. given the high mortality, clinical differences and the extensive ecological niche of cryptococcus neoformans and cryptococcus gattii species complexes, there is need for laboratories in sub-sahara african countries to adopt new and alternative reliable diagnostic algorithms that rapidly identify and dist ...201626661484
does the capsule interfere with performance of matrix-assisted laser desorption ionization-time of flight mass spectrometry for identification of cryptococcus neoformans and cryptococcus gattii?we described the impact of the capsule size for cryptococcus neoformans and cryptococcus gattii identification at the species level by bruker matrix-assisted laser desorption ionization-time of flight mass spectrometry (maldi-tof ms). after experimental capsule size modulation, we observed that reducing the capsule size resulted in improved identification by bruker maldi-tof ms across all of the reference strains analyzed.201626659203
the microcyclic conidial stage of coniochaeta pulveracea and its effect on selected biological interactions.coniochaeta pulveracea is a dimorphic lignicolous fungus that has mostly been isolated from decaying wood. however, relatively little work was conducted on the conditions for the dimorphic switch or the biological interactions of the fungus in its yeast-like microcyclic growth phase. therefore, in this study, the microcyclic conidiation of c. pulveracea strains and representatives of the closely related species, coniochaeta boothii and coniochaeta subcorticalis, was studied under different envir ...201626658947
cryptococcus neoformans capsular polysaccharides form branched and complex filamentous networks viewed by high-resolution microscopy.cryptococcus neoformans is a fungal pathogen that causes life-threatening infections in immunocompromised individuals. its main virulence factor is an extracellular polysaccharide capsule whose structure, assembly and dynamics remain poorly understood. in this study, we apply improved protocols for sample preparation and recently-developed scanning microscopy techniques to visualize the ultrastructure of the c. neoformans capsule at high-resolution (up to 1 nm) and improved structural preservati ...201626655746
microtubules and actin cytoskeleton of cryptococcus neoformans as targets for anticancer agents to potentiate a novel approach for new antifungals.we investigated the targeting of microtubules (mt) and f-actin cytoskeleton (ac) of the human pathogenic yeast cryptococcus neoformans with agents for cancer therapy, in order to examine whether this yeast cytoskeleton could become a new antifungal target for the inhibition of cell division.201626650399
inhibition of heat-shock protein 90 enhances the susceptibility to antifungals and reduces the virulence of cryptococcus neoformans/cryptococcus gattii species complex.heat-shock proteins (hsps) are chaperones required for the maintenance of cellular homeostasis in different fungal pathogens, playing an important role in the infectious process. this study investigated the effect of pharmacological inhibition of hsp90 by radicicol on the cryptococcus neoformans/cryptococcus gattii species complex--agents of the most common life-threatening fungal infection amongst immunocompromised patients. the influence of hsp90 inhibition was investigated regarding in vitro ...201626645478
secreted acb1 contributes to the yeast-to-hypha transition in cryptococcus neoformans.adaptation to stress by eukaryotic pathogens is often accompanied by a transition in cellular morphology. the human fungal pathogen cryptococcus neoformans is known to switch between the yeast and the filamentous form in response to amoebic predation or during mating. as in the classic dimorphic fungal pathogens, the morphotype is associated with the ability of cryptococci to infect various hosts. many cryptococcal factors and environmental stimuli, including pheromones (small peptides) and nutr ...201526637591
cryptococcal laryngitis: an uncommon presentation of a common pathogen.cryptococcus neoformans is an ubiquitous encapsulated yeast found worldwide, especially in areas with pigeons. the fungus thrives in pigeon droppings and is responsible for primary pulmonary infection, but may disseminate and cause infection of the central nervous system, skin and bone. most cases are reported in immunocompromised hosts, most commonly those infected with hiv. however, infection has been reported in immunocompetent hosts. primary infection of the larynx is uncommon, and to date o ...201526636155
[cryptococcal meningoencephalitis presenting with treatable cognitive impairment and involuntary movement].the patient is a 72-year-old japanese woman. seven years prior to admission, multiple nodules in her left lung were found. bronchoscopic biopsy of the nodules did not provide a confirmative diagnosis, and probable diagnosis of cryptococcosis was made. follow-up ct scan of the chest revealed reduction in size of the lung nodules. she was admitted to our hospital due to progressive cognitive impairment and difficulty in walking that lasted for 5 months. on admission, athetotic involuntary movement ...201626616484
successful treatment of cryptococcal meningitis with amphotericin b in a patient with systemic lupus erythematosus.patients with systemic lupus erythematosus (sle) have an increased susceptibility to bacterial, viral, fungal and parasitic infections. cryptococcal infection of the central nervous system (cns) is a rare but often fatal complication of sle. here, we describe a case of cryptococcal meningitis in a female patient with active sle, who was successfully treated with amphotericin b. this case suggests that the clinical findings of sle patients with cryptococcal meningitis are non-specific and mislead ...201528319250
what makes cryptococcus gattii a pathogen?cryptococcosis is an invasive fungal infection of humans and other animals, typically caused by the species cryptococcus neoformans in patients with impaired immunity. however, there is growing recognition of the importance of the related species c. gattii in causing infections in apparently immunocompetent individuals. in particular, an ongoing outbreak of cryptococcal disease in the pacific northwest region, which started in 1999, has driven an intense research effort into this previously negl ...201626614308
method for identification of cryptococcus neoformans and cryptococcus gattii useful in resource-limited settings.the high hiv/aids burden in sub-saharan africa has led to cryptococcosis becoming a public health concern. in this resource-limited setting, conventional identification methods are mainly used to diagnose cryptococcal infections. however, these methods are often inconsistent, and importantly, cannot discriminate between the aetiological agents, cryptococcus neoformans and c. gattii. therefore, there is a need for an alternative reliable method to identify these species.201626598625
all2, a homologue of all1, has a distinct role in regulating ph homeostasis in the pathogen cryptococcus neoformans.cryptococcus neoformans is a facultative intracellular fungal pathogen that has a polysaccharide capsule and causes life-threatening meningoencephalitis. its capsule, as well as its ability to survive in the acidic environment of the phagolysosome, contributes to the pathogen's resilience in the host environment. previously, we reported that downregulation of allergen 1 (all1) results in the secretion of a shorter, more viscous exopolysaccharide with less branching and structural complexity, as ...201526597983
role of dendritic cell-pathogen interactions in the immune response to pulmonary cryptococcal infection.this review discusses the unique contributions of dendritic cells (dcs) to t-cell priming and the generation of effective host defenses against cryptococcus neoformans (c.neo) infection. we highlight dc subsets involved in the early and later stages of anticryptococcal immune responses, interactions between c.neo pathogen-associated molecular patterns and pattern recognition receptors expressed by dc, and the influence of dc on adaptive immunity. we emphasize recent studies in mouse models of cr ...201526597428
occurrence and susceptibilities to disinfectants of cryptococcus neoformans in fecal droppings from pigeons in bangkok, thailand.cryptococcus neoformans is an opportunistic pathogenic yeast that causes meningoencephalitis and deep skin dermatitis in humans and animals. a hygienic strategy using disinfectants on environmental samples can reduce the risk to the public. the objectives were to survey the distribution of c. neoformans in pigeon fecal droppings collected in 11 districts in bangkok during 2011-2012 and to evaluate the efficacy of three commercial disinfectant products (based on potassium monopersulfate, sodium h ...201626596636
regulatory t cell induction and retention in the lungs drives suppression of detrimental type 2 th cells during pulmonary cryptococcal infection.lethal disease caused by the fungus cryptococcus neoformans is a consequence of the combined failure to control pulmonary fungal replication and immunopathology caused by induced type 2 th2 cell responses in animal models. in order to gain insights into immune regulatory networks, we examined the role of regulatory t (treg) cells in suppression of th2 cells using a mouse model of experimental cryptococcosis. upon pulmonary infection with cryptococcus, treg cells accumulated in the lung parenchym ...201626590316
the lncrna rze1 controls cryptococcal morphological transition.in the fungal pathogen cryptococcus neoformans, the switch from yeast to hypha is an important morphological process preceding the meiotic events during sexual development. morphotype is also known to be associated with cryptococcal virulence potential. previous studies identified the regulator znf2 as a key decision maker for hypha formation and as an anti-virulence factor. by a forward genetic screen, we discovered that a long non-coding rna (lncrna) rze1 functions upstream of znf2 in regulati ...201526588844
cryptococcus gattii in the age of whole-genome sequencing.cryptococcus gattii, the sister species of cryptococcus neoformans, is an emerging pathogen which gained importance in connection with the ongoing cryptococcosis outbreak on vancouver island. many molecular studies have divided this species into for major lineages: vgi, vgii, vgiii, and vgiv. this commentary summarizes the whole-genome sequencing (wgs) studies that have been carried out with this species, re-emphasizing the phylogenetic relationships, showing chromosomal rearrangements between t ...201526578680
transmembrane transporter expression regulated by the glucosylceramide pathway in cryptococcus neoformans.the sphingolipid glucosylceramide (glccer) and factors involved in the fungal glccer pathways were shown earlier to be an integral part of fungal virulence, especially in fungal replication at 37 °c, in neutral/alkaline ph and 5 % co2 environments (e.g. alveolar spaces). two mutants, ∆gcs 1 lacking glucosylceramide synthase 1 gene (gcs1) which catalyzes the formation of sphingolipid glccer from the c9-methyl ceramide and ∆smt1 lacking sphingolipid c9 methyltransferase gene (smt1), which adds a m ...201526572681
tor-dependent post-transcriptional regulation of autophagy.regulation of autophagy is required to maintain cellular equilibrium and prevent disease. while extensive study of post-translational mechanisms has yielded important insights into autophagy induction, less is known about post-transcriptional mechanisms that could potentiate homeostatic control. in our study, we showed that the rna-binding protein, dhh1 in saccharomyces cerevisiae and vad1 in the pathogenic yeast cryptococcus neoformans is involved in recruitment and degradation of key autophagy ...201526569496
spectrum of imaging appearances of intracranial cryptococcal infection in hiv/aids patients in the anti-retroviral therapy era.cryptococcus neoformans infection is the most common fungal infection of the central nervous system (cns) in advanced human immunodeficiency virus (hiv) and acquired immunodeficiency syndrome (aids) patients, but remains a relatively uncommon cns infection in both the immunocompromised and immunocompetent patient population, rendering it a somewhat elusive and frequently overlooked diagnosis. the morbidity and mortality associated with cns cryptococcal infection can be significantly reduced by e ...201626564776
refractory cryptococcus neoformans meningoencephalitis in an immunocompetent patient: paradoxical antifungal therapy-induced clinical deterioration related to an immune response to cryptococcal organisms.we present a case of refractory cryptococcus neoformans meningoencephalitis in an immunocompetent woman. her clinical symptoms did not improve with 6 months of antifungal therapy, and mri abnormalities, indicating severe meningeal and cerebral inflammation, persisted despite a decreasing cryptococcal antigen titer. the patient continued to deteriorate despite antifungal therapy, and her condition clearly improved following treatment with adjunctive corticosteroid. we postulate that the paradoxic ...201726557082
the il-33 receptor (st2) regulates early il-13 production in fungus-induced allergic airway inflammation.allergic airway inflammation (aai) in response to environmental antigens is an increasing medical problem, especially in the western world. type 2 interleukins (il) are central in the pathological response but their importance and cellular source(s) often rely on the particular allergen. here, we highlight the cellular sources and regulation of the prototypic type 2 cytokine, il-13, during the establishment of aai in a fungal infection model using cryptococcus neoformans. il-13 reporter mice rev ...201626555705
genotypes of clinical and environmental isolates of cryptococcus neoformans and cryptococcus gattii in korea.multilocus sequence typing analysis was applied to determine the genotypes of 147 (137 clinical and 10 environmental) cryptococcus neoformans and three clinical cryptococcus gattii isolates from 1993 to 2014 in korea. among the 137 clinical isolates of c. neoformans, the most prevalent genotype was st5 (n = 131), followed by st31 (n = 5) and st127 (n = 1). three c. gattii strains were identified as st57, st7, and st113. all environmental isolates were identified as c. neoformans with two genotyp ...201526539057
clinical study of 23 pediatric patients with cryptococcosis.cryptococcus neoformans is a common opportunistic infection in adults with acquired immunodeficiency syndrome. however, limited data exist for pediatric patients. the aim of this study was to describe the clinical characteristics of cryptococcosis in pediatric patients.201526531262
seroprevalence of histoplasmosis in kampala, uganda.histoplasmosis is endemic to the midwestern united states, but cases have been reported nearly worldwide. a 1970 study found 3.8% skin test sensitivity to histoplasma capsulatum in uganda but no systemic study of histoplasmosis exposure has occurred since the onset of the human immunodeficiency virus (hiv) pandemic. this study investigated the seroprevalence of h. capsulatum and sought previously undetected cases of histoplasmosis in kampala, uganda. serum, cerebrospinal fluid (csf) and/or urine ...201626527637
structure of a fungal form of aspartate semialdehyde dehydrogenase from cryptococcus neoformans.aspartate semialdehyde dehydrogenase (asadh) functions at a critical junction in the aspartate-biosynthetic pathway and represents a valid target for antimicrobial drug design. this enzyme catalyzes the nadph-dependent reductive dephosphorylation of β-aspartyl phosphate to produce the key intermediate aspartate semialdehyde. production of this intermediate represents the first committed step in the biosynthesis of the essential amino acids methionine, isoleucine and threonine in fungi, and also ...201526527262
cryptococcosis in atlántico, colombia: an approximation of the prevalence of this mycosis and the distribution of the etiological agent in the environment.cryptococcosis is an invasive disease acquired by inhalation of infectious propagules from the environment. currently, compulsory notification of the spread of this disease is not required in colombia. however, reporting of human immunodeficiency virus (hiv)/acquired immune deficiency syndrome cases to the national surveillance system has suggested that there is a growing population at risk of contracting cryptococcosis. few studies have described the occurrence of cryptococcosis in colombia. th ...201526516968
[cryptococcosis during hiv infection].cryptococcosis is a cosmopolitan fungal serious condition due to an encapsulated yeast cryptococcus neoformans. this is the systemic fungal infection the most common in hiv infection. this yeast is present in the environment and its main entrance in the body is the respiratory tract. its gravity is linked to its tropism for the central nervous system. it generally affects subjects with severe deficit of cellular immunity and in particular, patients living with hiv. the diagnosis of neuromeningea ...201526515783
isolation, identification and screening of antimicrobial thermophilic streptomyces sp. al-dhabi-1 isolated from tharban hot spring, saudi arabia.the strain streptomyces sp. al-dhabi-1 was isolated from soil sediments collected from tharban hot spring in the southern west of saudi arabia using actinomycetes isolation agar and starch casein agar at 55 °c. identification of the isolate was done according to morphological, physiological and biochemical characteristics and 16s rrna sequence similarity as well. 16s rrna sequence and blast analyses confirmed that the isolate belonging to the genus streptomyces. the sequence was submitted to gen ...201626515082
cryptococcal panniculitis in a renal transplant recipient: case report and review of literature.cryptococcosis is a deep fungal infection caused by cryptococcus neoformans. the infection usually involves the lungs, the central nervous system as well as the skin, the bones and the urinary tract. immunocompromised individuals, including solid organ transplant recipients, are at higher risk for cryptococcal infections.201526512304
hyponatremia as the initial presentation of cryptococcal meningitis after liver transplantation.meningoencephalitis is the most common clinical manifestation of cryptococcal infection, as the organism has a propensity to invade the cns. patients often present with elevated intracranial pressure, focal motor deficits, altered mentation and internal hydrocephalus. syndrome of inappropriate antidiuretic hormone secretion (siadh) has been reported as a notable cause of euvolemic hyponatremia in immunocompromised patients.201526504469
real-time imaging of interactions of neutrophils with cryptococcus neoformans demonstrates a crucial role of complement c5a-c5ar signaling.neutrophils have been shown to efficiently kill cryptococcus neoformans, a causative agent of meningoencephalitis. here, using live-cell imaging, we characterize the dynamic interactions of neutrophils with c. neoformans and the underlying mechanisms in real time. neutrophils were directly seen to chase c. neoformans cells and then rapidly internalize them. complement c5a-c5ar signaling guided neutrophils to migrate to the yeast cells, resulting in optimal phagocytosis and subsequent killing of ...201526502909
commentary: role of sterylglucosidase 1 (sgl1) on the pathogenicity of cryptococcus neoformans: potential applications for vaccine development. 201526500643
dark chemical matter as a promising starting point for drug lead discovery.high-throughput screening (hts) is an integral part of early drug discovery. herein, we focused on those small molecules in a screening collection that have never shown biological activity despite having been exhaustively tested in hts assays. these compounds are referred to as 'dark chemical matter' (dcm). we quantified dcm, validated it in quality control experiments, described its physicochemical properties and mapped it into chemical space. through analysis of prospective reporter-gene assay ...201526479441
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