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capsular polysaccharides from cryptococcus neoformans modulate production of neutrophil extracellular traps (nets) by human neutrophils.in the present study, we characterized the in vitro modulation of nets (neutrophil extracellular traps) induced in human neutrophils by the opportunistic fungus cryptococcus neoformans, evaluating the participation of capsular polysaccharides glucuronoxylomanan (gxm) and glucuronoxylomannogalactan (gxmgal) in this phenomenon. the mutant acapsular strain cap67 and the capsular polysaccharide gxmgal induced net production. in contrast, the wild-type strain and the major polysaccharide gxm did not ...201525620354
postpartum cryptococcal pulmonary lesion incidentally discovered during a pulmonary-embolism evaluation of a 28-year-old caucasian woman.we report a case of localized pulmonary cryptococcal infection in a 28-year-old caucasian woman who was 1 month postpartum at the time of her arrival at the hospital. the patient reported right-side chest pain; on further work up, she was found to have an incidental pulmonary lesion of the left lower lung lobe. surgical pathology examination and microbiology studies revealed localized cryptococcal infection. cases of cryptococcal pneumonia in pregnant women and in the postpartum period have been ...201525617397
cryptococcal phospholipase b1 is required for intracellular proliferation and control of titan cell morphology during macrophage infection.cryptococcus neoformans is an opportunistic fungal pathogen and a leading cause of fungal-infection-related fatalities, especially in immunocompromised hosts. several virulence factors are known to play a major role in the pathogenesis of cryptococcal infections, including the enzyme phospholipase b1 (plb1). compared to other well-studied cryptococcus neoformans virulence factors such as the polysaccharide capsule and melanin production, very little is known about the contribution of plb1 to cry ...201525605772
application of the diversilab system for tracing the source of the mixed infections caused by cryptococcus neoformans var. grubii from a patient with systemic lupus erythematosus.two strains of cryptococcus neoformans (pu 66 and pu112) were simultaneously isolated from a patient with systemic lupus erythematosus. we aimed to trace the source of the mixed infections. multi-locus sequence typing (mlst) and the diversilab system analyses were performed on the 2 clinical and 23 environmental c. neoformans from pigeon droppings, 11 from the home (h1) the patient visited, 12 from another home (h2) as control. all the strains were uniformly genotyped as c. neoformans var. grubi ...201525591136
utility of bone marrow examination for workup of fever of unknown origin in patients with hiv/aids.the utility of bone marrow aspiration and biopsy (bmab) as a diagnostic tool in patients with hiv/aids and fever of unknown origin (fuo) is a subject of debate. because highly active antiretroviral therapy has reduced incidence of opportunistic infections, it is important to reassess the efficacy of bmab for this diagnostic purpose. to our knowledge, no such studies have been performed in harris county which has the highest incidence of hiv in the state of texas.201525589792
distribution of yeast isolates from invasive infections and their in vitro susceptibility to antifungal agents: evidence from 299 cases in a 3-year (2010 to 2012) surveillance study.invasive yeast infections cause significant morbidity and mortality. surveillance for the infection is necessary to detect trends in species distribution and antifungal resistance. we performed this retrospective study of yeast infection at jinling hospital, nanjing in china, from year of 2010 to 2012. a total of 341 yeast isolates were obtained from patients with invasive infections in the period. among these isolates, candida spp. comprised of the highest percentage of yeast strains (91.8 %), ...201525588889
mitochondrial dna inheritance in the human fungal pathogen cryptococcus gattii.the inheritance of mitochondrial dna (mtdna) is predominantly uniparental in most sexual eukaryotes. in this study, we examined the mitochondrial inheritance pattern of cryptococcus gattii, a basidiomycetous yeast responsible for the recent and ongoing outbreak of cryptococcal infections in the us pacific northwest and british columbia (especially vancouver island) in canada. using molecular markers, we analyzed the inheritance of mtdna in 14 crosses between strains within and between divergent ...201525577978
antifungal activity of the essential oil of angelica major against candida, cryptococcus, aspergillus and dermatophyte species.the composition and antifungal activity of the essential oil (eo) of angelica major and its main components α-pinene and cis-β-ocimene against clinically relevant yeasts and moulds were evaluated. eo from the plant's aerial parts was obtained by hydrodistillation and analysed by gas chromatography (gc) and gas chromatography/mass spectrometry (gc/ms). the oil showed high contents of α-pinene (21.8 %) and cis-β-ocimene (30.4 %). minimum inhibitory concentrations (mics) were measured according to ...201525576097
primary cutaneous cryptococcosis in an eight-year-old immunocompetent child: how to treat?here we report on a case of primary cryptococcal skin infection in an immunocompetent 8-year-old boy. the infection first manifested itself as a subcutaneous abscess around the proximal joint of his right thumb after a minor injury from contact with a thorny shrub. after surgical incision and drainage was performed, cryptococcus neoformans var. neoformans was the only pathogen cultured from the lesion. an agglutination test for the capsular antigen in serum displayed negative results and the imm ...201525565197
a case of miliary pulmonary cryptococcosis and review of literature.we describe a case of cryptococcal fungemia in a 62-year-old male renal transplant patient. the diagnosis was established by isolation of cryptococcus neoformans using the isolator(®) blood culture lysis-centrifugation system. testing for cryptococcal antigens was negative in the serum and cerebrospinal fluid. transbronchial lung biopsies and bronchoalveolar lavage were negative. antifungal therapy with fluconazole was started, resulting in fever remission, and a sustained clinical response was ...201525563716
molecular characterization and antifungal susceptibility of cryptococcus neoformans strains collected from a single institution in lima, peru.cryptococcosis is a fungal infection with a worldwide distribution, mainly caused by cryptococcus neoformans and cryptococcus gattii.201525556051
leu1 plays a role in iron metabolism and is required for virulence in cryptococcus neoformans.amino acid biosynthetic pathways that are absent in mammals are considered an attractive target for antifungal therapy. leucine biosynthesis is one such target pathway, consisting of a five-step conversion process starting from the valine precursor 2-keto-isovalerate. isopropylmalate dehydrogenase (leu1) is an fe-s cluster protein that is required for leucine biosynthesis in the model fungus saccharomyces cerevisiae. the human pathogenic fungus cryptococcus neoformans possesses an ortholog of s. ...201525554701
is cryptococcus gattii a primary pathogen?the two etiologic agents of cryptococcal meningoencephalitis, cryptococcus neoformans and c. gattii, have been commonly designated as either an opportunistic pathogen for the first species or as a primary pathogen for the second species. such a distinction has been based on epidemiological findings that the majority of patients presenting meningoencephalitis caused by c. neoformans are immunocompromised while c. gattii infection has been reported more often in immunocompetent patients. a recent ...201527795955
infectious lymphadenitis in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma: a rare, but important, complication.the differential diagnosis of rapidly progressive or symptomatic lymphadenopathy in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (cll) includes infectious lymphadenitis. we studied 286 (9%) of 3040 patients with cll seen between 2003 and 2012 at mayo clinic rochester who had 356 diagnostic lymph node biopsies to evaluate rapidly progressive or symptomatic lymphadenopathy. most (85.4%) biopsies showed progressive cll, 8.9% a second lymphoid malignancy, 3.9% infectious lym ...201524738974
virulence mechanisms and cryptococcus neoformans pathogenesis.the human fungal pathogen cryptococcus neoformans is able to rapidly and effectively adapt to varying conditions, favoring its survival in the environment and in the infected host. many microbial phenotypes have been specifically correlated with virulence in this opportunistic pathogen, such as capsule production, melanin formation, and the secretion of various proteins. additionally, cellular features such as the cell wall and morphogenesis play important roles in the interaction of this fungus ...201525256589
breakthrough disseminated cryptococcosis during micafungin therapy.echinocandins are not active against basidiomycetous yeasts, such as cryptococcus neoformans, trichosporon, and rhodotorula species, and zygomycosis. we present a patient with renal failure and candidemia, who developed a breakthrough fungal infection with cryptococcemia and cryptococcuria while receiving micafungin therapy.201523632603
case report: false negative serum cryptococcal latex agglutination test in a patient with disseminated cryptococcal disease.a case of false-negative serum latex agglutination cryptococcal antigen (crag) test in a 45-year-old hiv-positive male with cryptococcus-positive culture is described. the patient was presented to a hospital in botswana, with breathlessness and a diffuse papular rash. his cd4 count was 25 cells/μl. despite the suspicion for disseminated cryptococcal disease, an initial serum crag latex test was negative. results of subsequent indian ink staining, culture of cerebrospinal fluid and skin scrapings ...201625331223
rna biology and the adaptation of cryptococcus neoformans to host temperature and stress.cryptococcus neoformans is an environmental fungus that can cause severe disease in humans. c. neoformans encounters a multitude of stresses within the human host to which it must adapt in order to survive and proliferate. upon stressful changes in the external milieu, c. neoformans must reprogram its gene expression to properly respond to and combat stress in order to maintain homeostasis. several studies have investigated the changes that occur in response to these stresses to begin to unravel ...201624497369
[intestinal cryptococcosis: an unusual presentation of disseminated cryptococcosis].cryptococcosis is a serious infection caused by an encapsulated yeast-like fungus, cryptococcus neoformans. it is pathogenic most often in the lungs and central nervous system of immunocompromised patients. in this work we report an unusual localization of cryptococcosis in an hiv-infected patient. this rare localization was diagnosed from a stool sample sent to our laboratory for parasitological study. direct examination of fresh stool showed the presence of many large, rounded thick-walled fun ...201624876169
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
[causes of lymphocytic meningitis in people with hiv admitted to the infectious disease department of conakry].the advent of hiv infection has significantly changed the distribution of the causes of lymphocytic meningitis. the objective of this study was to identify these causes among persons with hiv hospitalized in the infectious disease department of the chu of conakry.201625466555
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
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
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
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
[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
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
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
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
cryptococcus neoformans population diversity and clinical outcomes of hiv-associated cryptococcal meningitis patients in zimbabwe.hiv and cryptococcal meningitis co-infection is a major public health problem in most developing countries. cryptococcus neoformans sensu stricto is responsible for the majority of hiv-associated cryptococcosis cases in sub-saharan africa. despite the available information, little is known about cryptococcal population diversity and its association with clinical outcomes in patients with hiv-associated cryptococcal meningitis in sub-saharan africa. in a prospective cohort, we investigated the pr ...201627638836
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
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
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
role of laccase in the virulence of talaromyces marneffei: a common link between aids-related fungal pathogens? 201627282335
pd@ag nanosheets in combination with amphotericin b exert a potent anti-cryptococcal fungicidal effect.silver nanoparticles have received considerable interest as new "nanoantibiotics" with the potential to kill drug-resistant microorganisms. recently, a class of new core-shell nanostructures, pd@ag nanosheets (pd@ag nss), were created using deposition techniques and demonstrated excellent inhibitory effects on various bacteria in vitro. in this study, we evaluated the antifungal activity of pd@ag nss against common invasive fungal pathogens. among these organisms, cryptococcus neoformans complex ...201627271376
custom-made quorum sensing for a eukaryote.quorum-sensing systems, common in prokaryotes, enable bacteria to coordinately regulate behavior with population density. reporting recently in cell host & microbe, homer et al. (2016) characterize an elegant eukaryotic quorum-sensing pathway in the human pathogenic fungus cryptococcus neoformans.201627270036
repurposing of aspirin and ibuprofen as candidate anti-cryptococcus drugs.the usage of fluconazole and amphotericin b in clinical settings is often limited by, among other things, drug resistance development and undesired side effects. thus, there is a constant need to find new drugs to better manage fungal infections. toward this end, the study described in this paper considered the repurposing of aspirin (acetylsalicylic acid) and ibuprofen as alternative drugs to control the growth of cryptococcal cells. in vitro susceptibility tests, including a checkerboard assay ...201627246782
modulation of macrophage inflammatory nuclear factor κb (nf-κb) signaling by intracellular cryptococcus neoformans.cryptococcus neoformans (cn) is a common facultative intracellular pathogen that can cause life-threatening fungal meningitis in immunocompromised individuals. shortly after infection, cn is detectable as both extra- and intracellular yeast particles, with cn being capable of establishing long-lasting latent infections within host macrophages. although recent studies have shown that shed capsular polysaccharides and intact extracellular cn can compromise macrophage function through modulation of ...201627231343
investigation of the antifungal activity of carvacrol against strains of cryptococcus neoformans.cryptococcus neoformans is the etiologic agent of opportunistic systemic fungal infection cryptococcosis, which affects individuals with compromised immune systems. thus, natural products research has become important, since monoterpenes such as carvacrol, a promising molecule in the search antifungal agents, have shown significant biological activity.201627225838
intracellular action of a secreted peptide required for fungal virulence.quorum sensing (qs) is a bacterial communication mechanism in which secreted signaling molecules impact population function and gene expression. qs-like phenomena have been reported in eukaryotes with largely unknown contributing molecules, functions, and mechanisms. we identify qsp1, a secreted peptide, as a central signaling molecule that regulates virulence in the fungal pathogen cryptococcus neoformans. qsp1 is a direct target of three transcription factors required for virulence, and qsp1δ ...201627212659
reversible hearing loss following cryptococcal meningitis: case study.sensorineural hearing loss is a recognised complication of cryptococcal meningitis. the mechanism of hearing loss in patients with cryptococcal meningitis is different from that in bacterial meningitis.201627210482
environmental distribution of cryptococcus neoformans and c. gattii around the mediterranean basin.in order to elucidate the distribution of cryptococcus neoformans and c. gattii in the mediterranean basin, an extensive environmental survey was carried out during 2012-2015. a total of 302 sites located in 12 countries were sampled, 6436 samples from 3765 trees were collected and 5% of trees were found to be colonized by cryptococcal yeasts. cryptococcus neoformans was isolated from 177 trees and c. gattii from 13. cryptococcus neoformans colonized 27% of ceratonia, 10% of olea, platanus and p ...201627188887
molecular characterization of environmental cryptococcus neoformans vnii isolates in jos, plateau state, nigeria.cryptococcus neoformans and cryptococcus gattii are encapsulated yeasts able to cause fatal neurological infections in both human and other mammals. cryptococcosis is the most common fungal infection of the central nervous system and has a huge burden in sub-saharan africa and south east asia. bird excreta are considered an environmental reservoir for c. neoformans in urban areas, therefore a study aimed at isolating and characterizing this yeast is important in disease management. in this study ...201627184613
[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
a 'suicide' crispr-cas9 system to promote gene deletion and restoration by electroporation in cryptococcus neoformans.loss-of-function mutagenesis is an important tool used to characterize gene functions, and the crispr-cas9 system is a powerful method for performing targeted mutagenesis in organisms that present low recombination frequencies, such as the serotype d strains of cryptococcus neoformans. however, when the crispr-cas9 system persists in the host cells, off-target effects and cas9 cytotoxicity may occur, which might block subsequent genetic manipulation. here, we report a method of spontaneously eli ...201627503169
etiology and clinical features of 229 cases of bloodstream infection among chinese hiv/aids patients: a retrospective cross-sectional study.bloodstream infections (bsis) are prevalent among people living with hiv/aids. the etiology varies in different regions and different periods. we aimed to survey the etiological and clinical features of bsis in hiv patients in mainland china. we assessed all hiv patients with a positive blood culture in a chinese teaching hospital from september 2009 through december 2014. we excluded those with specimens likely to have been contaminated. we used pearson's chi-squared test to measure the differe ...201627502930
risk factors for cryptococcal meningitis: a single united states center experience.cryptococcal meningitis carries a high mortality. further understanding of immune suppression factors associated with neuroinvasive infection will improve risk stratification and enhance early diagnosis and treatment with antifungal therapy. the aim of the study was to corroborate established or find novel clinical predictors for cryptococcal meningitis. we performed a matched case-control study of cryptococcus infection in immunocompromised patients with or without cryptococcal meningitis. data ...201627502502
a case of cryptococcus neoformans meningitis in a patient with abnormal levels of isolated immunological markers.cryptococcal meningitis is considered rare in immunocompetent patients and is mainly a disease of immunocompromised patients. we report a case of cryptococcal meningitis, due to cryptococcus neoformans, in an apparently healthy individual with abnormal levels of isolated immunological markers. regardless of the patient's immune status, the result of the disease can be serious unless the disease is diagnosed early.201627402508
neutrophil swarming toward cryptococcus neoformans is mediated by complement and leukotriene b4.swarming behavior of neutrophils has been noticed in both sterile injury and infection models and the mechanisms are being unveiled. so far, no in vitro model has been established to study neutrophil swarming to microbes. in the current study, using live-cell imaging, we observed in vitro neutrophil swarming toward cryptococcus neoformans, a fungal pathogen causing human meningoencephalitis. complement c3 and cd11b expression are essential for neutrophils to form cell swarms surrounding c. neofo ...201627402276
opposing pka and hog1 signals control the post-transcriptional response to glucose availability in cryptococcus neoformans.the pathogenic fungus cryptococcus neoformans must adapt to glucose-limited conditions in the lung and glucose replete conditions upon dissemination to the brain. we report that glucose controls ribosome biogenesis and translation by modulating mrna decay through a balance of pka and hog1 signalling. glucose signalling through pka stabilized ribosomal protein (rp) mrnas whereas glucose starvation destabilized rp transcripts through hog1. glucose starvation-induced oxidative stress response genes ...201627387858
identification of qtls associated with virulence related traits and drug resistance in cryptococcus neoformans.cryptococcus neoformans is a basidiomycete fungus capable of causing deadly meningoenchephilitis, primarily in immunocompromised individuals. formerly, c. neoformans was composed of two divergent lineages, but these have recently been elevated to species status, now c. neoformans (formerly c. neoformans var. grubii) and c. deneoformans (formerly c. neoformans var. neoformans). while both species can cause deadly infections in humans, c. neoformans is much more prevalent in clinical settings than ...201627371951
the membrane phospholipid binding protein annexin a2 promotes phagocytosis and nonlytic exocytosis of cryptococcus neoformans and impacts survival in fungal infection.cryptococcus neoformans is a fungal pathogen with a unique intracellular pathogenic strategy that includes nonlytic exocytosis, a phenomenon whereby fungal cells are expunged from macrophages without lysing the host cell. the exact mechanism and specific proteins involved in this process have yet to be completely defined. using murine macrophages deficient in the membrane phospholipid binding protein, annexin a2 (anxa2), we observed a significant decrease in both phagocytosis of yeast cells and ...201627371724
the lysine biosynthetic enzyme lys4 influences iron metabolism, mitochondrial function and virulence in cryptococcus neoformans.the lysine biosynthesis pathway via α-aminoadipate in fungi is considered an attractive target for antifungal drugs due to its absence in mammalian hosts. the iron-sulfur cluster-containing enzyme homoaconitase converts homocitrate to homoisocitrate in the lysine biosynthetic pathway, and is encoded by lys4 in the model yeast saccharomyces cerevisiae. in this study, we identified the ortholog of lys4 in the human fungal pathogen, cryptococcus neoformans, and found that lys4 expression is regulat ...201627353379
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