Amplified fragment length polymorphism (AFLP) genotyping of isolates of the pathogenic fungus Cryptococcus neoformans suggested a considerable genetic divergence between the varieties C. neoformans var. neoformans and C. neoformans var. grubii on the one hand versus C. neoformans var. gattii on the other. This divergence is supported by additional phenotypic, biochemical, clinical and molecular differences. Therefore, the authors propose the existence of two species, C. neoformans (Sanfelice) Vuillemin and C. bacillisporus Kwon-Chung, which differ in geographical distribution, serotypes and ecological origin. Within each species three AFLP genotypes occur, which differ in geographical distribution and serotypes. Differences in ecological origin (AIDS patients, non-AIDS patients, animals or the environment) were found to be statistically not significant. In C. neoformans as well as in C. bacillisporus one of the genotypes represented a hybrid. The occurrence of hybridization has consequences for the
The lysis of infected cells by disease-causing microorganisms is an efficient but risky strategy for disseminated infection, as it exposes the pathogen to the full repertoire of the hosts immune system. Cryptococcus neoformans is a widespread fungal pathogen that causes a fatal meningitis in HIV and other immunocompromised patients. Following intracellular growth, cryptococci are able to escape their host cells by a non-lytic expulsive mechanism that may contribute to the invasion of the central nervous system. Non-lytic escape is also exhibited by some bacterial pathogens and is likely to facilitate long-term avoidance of the host immune system during latency. Here we show that phagosomes containing intracellular cryptococci undergo repeated cycles of actin polymerisation. These actin flashes occur in both murine and human macrophages and are dependent on classical WASP-Arp2/3 complex mediated actin filament nucleation. Three dimensional confocal imaging time lapse revealed that such flashes ...
MELO, Natalina Takahashi de et al. Biotyping of Cryptococcus neoformans. Review of the literature. New epidemiologic informations about cryptococcosis. Our experience with the utilization of C.G.B medium in this yeast. Rev. Inst. Med. trop. S. Paulo [online]. 1993, vol.35, n.5, pp.469-478. ISSN 1678-9946. http://dx.doi.org/10.1590/S0036-46651993000500015.. The purpose of this work was to collect the main information from the literature about the biotyping of Cryptococcus neoformans. The more up-to date research concerning the epidemiology of cryptococcosis comprising quite a few articles, mainly after the advent of AIDS, was also reviewed. The Cryptococcus neoformans varieties neoformans and gattii are well defined biochemically nowadays chiefly through the C.G.B. medium, according to KWON-CHUNG et al. (1982)24. The isolation of C. neoformans var. gattii from flowers and leaves of Eucalyptus camaldulensis and Eucalyptus tereticornis, specially in Australia, through the works of ELLIS & PFEIFFER ...
Cryptococcus neoformans var. grubii ATCC ® 208821D-2™ Designation: Genomic DNA from Cryptococcus neoformans var. grubii strain H99JP [ATCC ® 208821™] Application:
TY - JOUR. T1 - The membrane phospholipid binding protein annexin A2 promotes phagocytosis and nonlytic exocytosis of cryptococcus neoformans and impacts survival in fungal infection. AU - Stukes, Sabriya. AU - Coelho, Carolina. AU - Rivera, Johanna. AU - Jedlicka, Anne E.. AU - Hajjar, Katherine A.. AU - Casadevall, Arturo. PY - 2016/8/15. Y1 - 2016/8/15. N2 - 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 the frequency of nonlytic exocytosis. Cryptococcal cells isolated from Anxa2-deficient (Anxa2-/-) bone marrow-derived macrophages and lung ...
Cryptococcus neoformans serotype A is responsible for the majority of cryptococcal infections in AIDS patients. In France, approximately 17% of the patients
TY - JOUR. T1 - Antibody-mediated protection in murine Cryptococcus neoformans infection is associated with pleotrophic effects on cytokine and leukocyte responses. AU - Feldmesser, Marta. AU - Mednick, Aron. AU - Casadevall, Arturo. PY - 2002. Y1 - 2002. N2 - Cryptococcus neoformans, an encapsulated yeast, is a common cause of life-threatening meningoencephalitis in immunosuppressed patients. We previously observed that administration of a monoclonal antibody (MAb) to the capsular polysaccharide to mice with pulmonary infection prolonged survival and enhanced granulomatous inflammation without reducing lung CFU. To understand the mechanism of MAb action, we studied leukocyte recruitment and cytokine profiles in lungs of A/JCr mice. B lymphocytes were the predominant cell type in lung infiltrates, comprising 15 to 30% of the leukocytes. Despite alterations in histological appearance, fluorescence-activated cell sorter analysis revealed no significant difference in total numbers of lung ...
Strains and cell growth: C. neoformans was grown with continuous shaking at 30° in YPD medium [1% (w/v) Bacto yeast extract; 2% (w/v) peptone, 2% dextrose] or minimal medium lacking uracil (Ausubelet al. 2001). Low adenine plates contained yeast nitrogen base supplemented with (per liter) 20 g glucose; 24 mg uracil; 40 mg each arginine, histidine, isoleucine, leucine, lysine, methionine, and tryrosine; 60 mg phenylalanine and tryptophan; 120 mg homoserine; 180 mg valine; and 10 mg adenine. For experiments using 5-fluoroorotic acid (5-FOA), plates contained the same medium with adenine raised to 40 mg/liter and the addition of 1 g/liter 5-FOA. Wild-type serotype D strain B4500 and cap59 strain TYCC33 (Chang and Kwon-Chung 1994) were from Dr. June Kwon-Chung (National Institutes of Health), and ura5 strain JEC43 (Wickeset al. 1997) was from Dr. Joseph Heitman (Duke University Medical Center). JEC43 cells transformed with a control plasmid alone (CIP-GUST.Cla.Kpn; see below) are designated ...
We have recently identified peptide mimetics of the Cryptococcus neoformans capsular polysaccharide by screening phage display peptide libraries. 2H1, one of a large family of mAbs against the glucuronoxylomannan fraction (GXM), is highly protective and binds several peptide motifs. This study analyzes the immunologic properties of P601E (SYSWMYE), a peptide from the low affinity motif (W/YXWM/LYE) that has an extended cross-reactivity among anti-GXM mAbs and whose binding correlates with the protective potential of mAbs in experimental infection. P601E is a mimetic, since it competes for GXM binding to 2H1, but not a mimotope, since it does not elicit an anti-GXM response. Sequence analysis of 14 anti-P601E mAbs indicates that anti-P601E mAbs elicited in BALB/c mice have an order of homology with 2H1 of V kappa | J kappa || V(H) | J(H) | D. Further screening of a peptide library with anti-P601E mAbs isolated peptides having a motif almost identical to the peptide motif selected by 2H1. When these
A polysaccharide capsule is one of the most important virulence factors for the pathogenic fungus Cryptococcus neoformans. We previously characterized two capsule-associated genes,CAP59 and CAP64. To further dissect the molecular mechanism of capsule synthesis, 16 acapsular mutants induced by 4-nitroquinoline-1-oxide were obtained. The acapsular phenotype of one of these mutants was complemented. The cloned gene was designatedCAP60, and deletion of this newly described capsule-associated gene resulted in an acapsular phenotype. The proposed 67-kDa Cap60p contains 592 amino acids and appears to have a putative transmembrane domain close to the N terminus. DNA sequence analysis revealed that CAP60 has similarity toCAP59 at the center portion of its coding regions. Contour-clamped homogeneous electric field blot analysis suggested that these two genes are on the same chromosome. CAP60 andCAP59, however, could not be functionally substituted for each other by direct complementation or by domain swap ...
TY - JOUR. T1 - Immunoglobulin G monoclonal antibodies to Cryptococcus neoformans protect mice deficient in complement component C3. AU - Shapiro, Scott. AU - Beenhouwer, David O.. AU - Feldmesser, Marta. AU - Taborda, Carlos. AU - Carroll, Michael C.. AU - Casadevall, Arturo. AU - Scharff, Matthew D.. PY - 2002. Y1 - 2002. N2 - Passive administration of monoclonal antibodies (MAbs) to the capsular polysaccharide of Cryptococcus neoformans can alter the course of infection in mice. In a murine model of cryptococcal infection, immunoglobulin G1 (IgG1), IgG2a, and IgG2b switch variants of the anti-capsular 3E5 MAb prolong the survival of lethally infected mice, whereas the 3E5 IgG3 MAb does not protect and in some cases enhances infection, shortening the life spans of infected mice. We examined the role of complement component C3 in Ab-mediated protection by determining the efficacy of the four mouse IgG subclasses against C. neoformans in mice genetically deficient in factor C3 as well as mice ...
Background Cryptococcus neoformans is a pathogenic yeast that causes cryptococcosis, a life threatening disease. The prevalence of cryptococcosis in Asia has been rising after the onset of the AIDS epidemic and estimates indicate more than 120 cases per 1,000 HIV-infected individuals per year. Almost all cryptococcal disease cases in both immunocompromised and immunocompetent patients in Asia are caused by C. neoformans var. grubii. Epidemiological studies on C. neoformans in pan-Asia have not been reported. The present work studies the genetic diversity of the fungus by microsatellite typing and susceptibility analysis of approximately 500 isolates from seven Asian countries. Methodology/Principal Findings Genetic diversity of Asian isolates of C. neoformans was determined using microsatellite analysis with nine microsatellite markers. The analysis revealed eight microsatellite complexes (MCs) which showed different distributions among geographically defined populations. A correlation between MCs and
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Unique clinical characteristics and other variables influencing the outcome of Cryptococcus neoformans infection in organ transplant recipients have not been well defined. From a review of published reports, we found that C. neoformans infection was documented in 2.8% of organ transplant recipients (overall death rate 42%). The type of primary immunosuppressive agent used in transplantation influenced the predominant clinical manifestation of cryptococcosis. Patients receiving tacrolimus were significantly less likely to have central nervous system involvement (78% versus 11%, p =0.001) and more likely to have skin, soft-tissue, and osteoarticular involvement (66% versus 21%, p = 0.006) than patients receiving nontacrolimus-based immunosuppression. Renal failure at admission was the only independently significant predictor of death in these patients (odds ratio 16.4, 95% CI 1.9 - 143, p = 0.004). Hypotheses based on these data may elucidate the pathogenesis and may ultimately guide the management of C.
Innate immunity plays an important role for fungal recognition and initiation of fungicidal activity. We hypothesize that subtle differences in different molecules of innate immunity may contribute to either the predisposition or clinical course of infection with Cryptococcus neoformans. To test this hypothesis, we propose to analyze the allelic frequencies of 15 different genes (mannose binding lectin, Fc-gamma receptor IIa and IIb, Fc-gamma receptors IIIa and IIIb, myeloperoxidase, tumor necrosis factor-alpha and -beta, interleukin 1A and 1B, interleukin-1 receptor antagonist, interleukin-10, NRAMP-1, chitotriosidase, and chemokine receptor 5) and their intragenic polymorphic forms and to compare this data to the incidence and severity of C neoformans infection. With this study we hope to identify a group of molecules of innate immunity which influence the risk and severity of invasive C neoformans infection ...
Innate immunity plays an important role for fungal recognition and initiation of fungicidal activity. We hypothesize that subtle differences in different molecules of innate immunity may contribute to either the predisposition or clinical course of infection with Cryptococcus neoformans. To test this hypothesis, we propose to analyze the allelic frequencies of 15 different genes (mannose binding lectin, Fc-gamma receptor IIa and IIb, Fc-gamma receptors IIIa and IIIb, myeloperoxidase, tumor necrosis factor-alpha and -beta, interleukin 1A and 1B, interleukin-1 receptor antagonist, interleukin-10, NRAMP-1, chitotriosidase, and chemokine receptor 5) and their intragenic polymorphic forms and to compare this data to the incidence and severity of C neoformans infection. With this study we hope to identify a group of molecules of innate immunity which influence the risk and severity of invasive C neoformans infection ...
TY - JOUR. T1 - Sre1p, a regulator of oxygen sensing and sterol homeostasis, is required for virulence in Cryptococcus neoformans. AU - Chang, Yun C.. AU - Bien, Clara M.. AU - Lee, Hyeseung. AU - Espenshade, Peter J.. AU - Kwon-Chung, Kyung J.. PY - 2007/5/1. Y1 - 2007/5/1. N2 - Cryptococcus neoformans is an environmental pathogen requiring atmospheric levels of oxygen for optimal growth. Upon inhalation, C. neoformans disseminates to the brain and causes meningoencephalitis, but the mechanisms by which the pathogen adapts to the low-oxygen environment in the brain have not been investigated. We found that SRE1, a homologue of the mammalian sterol regulatory element-binding protein (SREBP), functions in an oxygen-sensing pathway. Low oxygen decreased sterol synthesis in C. neoformans and triggered activation of membrane-bound Sre1p by the cleavage-activating protein, Scp1p. Microarray and Northern blot analysis demonstrated that under low oxygen, Sre1p activates genes required for ergosterol ...
Cryptococcus neoformans is a human-pathogenic fungus that has evolved into three distinct varieties that infect most prominently the central nervous system. A sexual cycle involving haploid cells of a and alpha mating types has been reported for two varieties (C. neoformans var. neoformans, serotype …
Infection wif C. neoformans is termed cryptococcosis. Most infections wif C. neoformans occur in de wungs.[12] However, fungaw meningitis and encephawitis, especiawwy as a secondary infection for AIDS patients, are often caused by C. neoformans, making it a particuwarwy dangerous fungus. Infections wif dis fungus are rare in dose wif fuwwy functioning immune systems.[13] So, C. neoformans is sometimes referred to as an opportunistic fungus.[13] It is a facuwtative intracewwuwar padogen[14] dat can utiwize host phagocytes to spread widin de body.[15][16] Cryptococcus neoformans was de first intracewwuwar padogen for which de non-wytic escape process termed vomocytosis was observed.[17][18] It has been specuwated dat dis abiwity to manipuwate host cewws resuwts from environmentaw sewective pressure by amoebae, a hypodesis first proposed by Arturo Casadevaww under de term "accidentaw viruwence".[19]. In human infection, C. neoformans is spread by inhawation of aerosowized basidiospores, and can ...
Eukaryota; Fungi; Dikarya; Basidiomycota; Agaricomycotina; Tremellomycetes; Tremellales; Cryptococcaceae; Cryptococcus; Cryptococcus neoformans species ...
Cryptococcus neoformans CAP59 protein: involved in capsule formation which is essential for virulence of Cryptococcus neoformans; amino acid sequence given in first source; GenBank L26508
Antibody-mediated defense against pathogens typically requires complex interactions between antibodies and other constituents of the humoral and cellular immune systems. However, recent evidence indicates that some antibodies alone can inhibit pathogen function in the absence of complement, phagocytes, or NK cells. In this issue of the JCI, McClelland et al. have begun to elucidate the molecular bases by which antibodies alone can impact pathogen growth and metabolism. They show that mAbs specific for the polysaccharide capsule of the human pathogenic fungus Cryptococcus neoformans elicit diverse effects on fungal gene expression, lipid biosynthesis, susceptibility to amphotericin B, cellular metabolism, and protein phosphorylation. These data suggest that pathogens have the capacity to generate broad metabolic responses as a result of surface binding by pathogen-specific antibodies, effects that may hold therapeutic promise. ...
Antibody-mediated defense against pathogens typically requires complex interactions between antibodies and other constituents of the humoral and cellular immune systems. However, recent evidence indicates that some antibodies alone can inhibit pathogen function in the absence of complement, phagocytes, or NK cells. In this issue of the JCI, McClelland et al. have begun to elucidate the molecular bases by which antibodies alone can impact pathogen growth and metabolism. They show that mAbs specific for the polysaccharide capsule of the human pathogenic fungus Cryptococcus neoformans elicit diverse effects on fungal gene expression, lipid biosynthesis, susceptibility to amphotericin B, cellular metabolism, and protein phosphorylation. These data suggest that pathogens have the capacity to generate broad metabolic responses as a result of surface binding by pathogen-specific antibodies, effects that may hold therapeutic promise. ...
Major histocompatibility complex (MHC) genes are unique in their general importance for conferring susceptibility or resistance to infectious and autoimmune diseases (5). It is unclear what keeps these demonstrably harmful genes from being eliminated by natural selection unless they provide some advantage, presumably against some other disease. The only way to unravel these interactions is to characterize the effects of MHC genes on a variety of pathogens and autoimmune diseases. The goal of this study was to experimentally test for an MHC-dependent susceptibility pattern during chronic Cryptococcus neoformans infections.. C. neoformans is a common, opportunistic pathogen that causes disease in immunocompromised individuals. Previous studies have found that various components of immunity are important in clearing a C. neoformans infection. These components include interleukin-12 (11), interleukin-18 (17), inducible nitric oxide synthase (2), gamma interferon (16), B cells (3), and T cells (7). ...
Cryptococcus neoformans (C. neoformans) is a major opportunistic fungal pathogen in individuals with impaired T cell-mediated immunity. Notch pathway is an important signaling component of immunological synapse during APC/T-cell engagement. Little is known about the role of Notch signaling in fungal infections. We sought to determine the role of Notch signaling in C. neoformans infection. Wild-type C57BL/6 (WT) and CD4-Cre+×ROSA DNMAML (DNMAML) mice were infected intratracheally infected with C. neoformans. The fungal burden, leukocyte recruitment, and cytokine profile were assessed at 3 and 6 weeks post-infection (wpi). A 50-fold greater fungal burden was detected in both lungs and brains of DNMAML mice compared to those in the WT mice at 6 wpi. Although, equivalent fungal burdens were found at 3 wpi in WT and DNMAML groups, the production of IFN-γ, IL-4, and IL-13 was significantly decreased in lung leukocytes of DNMAML mice. In contrast, an equivalent induction of IL-17 was observed in both ...
P. multocida is the causative agent of a wide range of diseases of animals, including fowl cholera in birds. Fowl cholera isolates of P. multocida generally express a capsular polysaccharide composed of hyaluronic acid. There have been reports of spontaneous capsule loss in P. multocida fowl cholera-causing strains but the mechanism by which this occurs has not been determined. In this study, we identified three independent strains that had spontaneously lost the ability to produce capsular polysaccharide. Quantitative RT-PCR showed that these strains had significantly reduced transcription of the capsule biosynthetic genes, but DNA sequence analysis identified no mutations within the cap biosynthetic locus. However, whole genome sequencing of paired capsulated and acapsular strains identified a single nucleotide polymorphism within fis that was present only in the acapsular strain. Sequencing of fis from two independently derived spontaneous acapsular strains showed that each contained a mutation
pathogen-associated molecular patterns (PAMP) are recognized by Toll-like receptors (TLR) and C-type lectin recptors including Dectin-1. Previously, we indicated that neither TLR2 nor TLR4 was involved in the host defence to infection with Cryptococcus neoformans, an opportunistic fungal pathogen in AIDS patients (FEMS Immunol. Med. Microbiol. 47: 148-154, 2006). In the current study, we examined the role of Dectin-1, a receptor for β-glucan, in this response. Dectin-1-deficient mice were resistant to intratracheal and intravenous infection with C. neoformans at a comparable level to wild-type mice. IFN-γ production in lung an serum was not largely different between these mice. There was not significant difference in the synthesis of IL-12p40 and TNF-α by bone marrow-derived dendritic cells upon stimulation with this fungal pathogen. Taken together, these results demonstrated that Dectin-1 did not play a major role in the host protective responses to C. neoformans infection.. This work was ...
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Definition : Molecular assay reagents intended to identify Cryptococcus neoformans, a yeast-like species of imperfect fungi of the family Cryptococcaceae, by detecting specific nucleic-acid information (e.g., DNA, RNA) of the target microorganism. These fungi may cause cryptococcosis, a mycotic infection of the brain and meninges, which may also involve other organs such as the skin and lungs. The disease may progress by invading the central nervous system, lungs, liver, and spleen of immunocompromised patients.. Entry Terms : "Cryptococcus Species Detection/Identification Reagents" , "Cryptococcus neoformans Reagents, Identification" , "Cryptococcus neoformans Detection/Identification Reagents" , "Reagents, Cryptococcus neoformans" , "Reagents, Molecular Assay, Infection, Fungi/Yeast, Cryptococcus neoformans". UMDC code : 19595 ...
Cryptococcus neoformans, a fungal pathogen of humans, causes fatal meningitis in immunocompromised patients. Its virulence is mainly determined by the elaboration of a polysaccharide capsule surrounding its cell wall. During its life, C. neoformans is confronted with and responds to dramatic variations in CO2 concentrations; one important morphological change triggered by the shift from its natural habitat (0.033% CO2) to infected hosts (5% CO2) is the induction of capsule biosynthesis. In cells, CO2 is hydrated to bicarbonate in a spontaneous reaction that is accelerated by carbonic anhydrases. Here we show that C. neoformans contains two beta-class carbonic anhydrases, Can1 and Can2. We further demonstrate that CAN2, but not CAN1, is abundantly expressed and essential for the growth of C. neoformans in its natural environment, where CO2 concentrations are limiting. Structural studies reveal that Can2 forms a homodimer in solution. Our data reveal Can2 to be the main carbonic anhydrase and ...
The population structure of a sample of clinical isolates of C. neoformans serotype A from AIDS patients in Botswana was determined, and the results support hypotheses for both clonal expansion and recombination in this population. Clonal reproduction was previously recognized in C. neoformans, as strains with identical genotypes were isolated from the environment and infected humans (5, 7, 16). The overrepresentation in the population of certain genotypes is a common feature of clonal structure (44). In the sample analyzed here, five genotypes comprised 45% of the total number of isolates (Fig. 4). Another indication of clonality is the calculation of considerable linkage disequilibrium (or nonrandom association) among the loci in the population. The IA and the rd are calculated estimates of linkage disequilibrium (or nonrandom association) among the loci; if there is no association between the loci, these values approach zero, whereas these values are much higher in clonal populations. When ...
Objectives: Cryptococcal meningitis is the third-most-common opportunistic infection in HIV patients in Cambodia. Hospitalized patients were given amphotericin B for initial therapy followed by fluconazole for maintenance therapy. The antifungal drug susceptibility of Cryptococcus neoformans isolated from cerebrospinal fluid (CSF) was determined.. Methods: Isolates of C. neoformans were collected during active laboratory-based surveillance, the first batch from April 2000 to March 2001 (134 new cases), the second batch from April 2001 to March 2002 (268 new cases). Etest strips were used to determine the MICs of amphotericin B and fluconazole. The antigenic agglutination slide test was used for serotyping.. Results: The MIC50s and MIC90s of fluconazole changed significantly from year 2000 to 2002; the MIC50s increased from 4 to 12 mg/L, and the MIC90s from 12 to 96 mg/L. For amphotericin B, the MIC50s and MIC90s remained stable. Moreover, in the second batch, fluconazole MICs were ≥256 mg/L ...
Pheromones and pheromone receptors have long been known to affect virulence of the opportunistic pathogen Cryptococcus neoformans, yet it is still entirely uncl...
Aritreyee Datta*, Vikas Yadav*, ............, Kaustuv Sanyal, Ayyalusamy Ramamoorthy and Anirban Bhunia, Mode of Action of a Designed Antimicrobial Peptide: High Efficiency in Killing of the Human Fungal Pathogen Cryptococcus neoformans, Biophysical Journal 111, 1724 - 1737 (2016 ...
Abstract: Cryptococcus neoformans is a spherical, encapsulated, basidiomycetous yeast and the causative agent of cryptococcosis, a form of meningitis that affects the central nervous system of immunocompromised individuals (immunocompromised means patients with compromised immune systems). Since the 1980s and the emergence of the AIDS epidemic, much study has been concentrated on this fungus because cryptococcosis is 100% fatal in untreated patients. Even with treatment, the condition does not always decrease in severity, and no major advancements in antifungal drugs have been made in a decade. Recently, Cryptococcus has been shown to possess the necessary machinery for RNA interference (RNAi). RNAi is a method of post-transcriptional gene silencing that may increase cryptococcal survival within mammalian hosts by controlling gene expression at various stages of the life cycle through heterochromatin and euchromatin rearrangement. RNAi was first described in Caenorhabditis elegans in 1998 by ...
Prx systems The Prx system is important for cellular processes associated with disulfide bond formation, the anti-oxidative stress response and pathogenesis of C. neoformans infection (47). Prxs, also known as thiol peroxidases, are 20-30 kDa-sized molecules that provide antioxidant protection by removing peroxides (47). Prxs may be classified into 1-Cys and 2-Cys subgroups (48). Following peroxidation, typical 2-Cys Prxs form homodimers through an intersubunit disulfide bridge, whereas atypical 2-Cys Prxs form an intramolecular disulfide bridge (48). By contrast, 1-Cys Prxs assume a monomeric form with a single active cysteine site (48). In a previous study, two Prxs, TSA1 and TSA3, were discovered in C. neoformans, of which TSA1 is highly conserved (48). In addition, the findings of Missall et al (48) indicated that Prxs were induced under oxidative and nitrosative stress and were critical for C. neoformans virulence in mice. Furthermore, their study demonstrated that deletion of TSA1, but not ...
The sexual cycle of C. neoformans has been studied for more than three decades, yet many aspects about the role of mating in the biology of this fungus remain to be resolved. One key example is a lack of knowledge about the events occurring in the basidium that result in nuclear reduction and the production of chains of spores, and the focus of this investigation. The ideal approach to examine spore production is a genetic one, i.e., by analyzing genetic markers in progeny derived from a single basidium. Just such an approach can be achieved by careful micromanipulation of the spores from the ends of basidia, and in this study the nature of the reductive event in the basidium is defined genetically by taking whole basidia and analyzing the phenotypes of all progeny.. Spores derived from 101 individual basidia were isolated and their phenotypes determined (Table 1). The data can be analyzed and interpreted in a number of ways: the interpretation placed here is that in a C. neoformans basidium ...
Cryptococcus neoformans is an environmental encapsulated yeast that behaves as an opportunistic pathogen in immunocompromised individuals. The capsule is the main virulence factor of this pathogen. This structure is highly dynamic, and it can change its size and structure according to the environmental conditions. During infection, C. neoformans significantly enlarges the size of the capsule by the addition of new polysaccharide. It is believed that capsule growth is an energy-cost process, but this aspect has never been addressed. In this work, we have evaluated the role of mitochondrial activity on capsule growth using specific inhibitors of the electron respiratory chain. We observed that capsule growth was impaired in the presence of inhibitors of the respiratory chain as salicylhydroxamic acid (SHAM) or antimycin A. Furthermore, capsule growth correlated with an increase of the mitochondrial membrane potential and higher production of reactive oxygen species. Our results confirm that capsule growth
Cryptococcosis, specifically caused by Cryptococcus neoformans, is a subacute or chronic fungal infection with several manifestations. It is commonly observed as a disseminated disease in the immunocompromised patient with approximately two thirds of patients experiencing meningitis.(3,5) Because of the wide spectrum of Cryptococcosis and the opportunistic nature of such infection, rapid laboratory identification of Cryptococcus neoformans is necessary so that therapy can be immediately initiated. The presumptive identification of Cryptococcus neoformans is based on the presence of an encapsulated yeast (using India ink), the absence of pseudohyphae, the failure to utilize an inorganic nitrate substance, and the ability to produce urease. The final identification of C. neoformans is usually based on typical substrate utilization patterns and brown pigment production in the presence of caffeic acid.(2,3,5). The brown pigmented colonies of Cryptococcus neoformans were observed by Staib in 1962 ...
The pathogenic species of Cryptococcus are a major cause of mortality owing to severe infections in immunocompromised as well as immunocompetent individuals. Although antifungal treatment is usually effective, many patients relapse after treatment, and in such cases, comparative analyses of the genomes of incident and relapse isolates may reveal evidence of determinative, microevolutionary changes within the host. Here, we analyzed serial isolates cultured from cerebrospinal fluid specimens of 18 South African patients with recurrent cryptococcal meningitis. The time between collection of the incident isolates and collection of the relapse isolates ranged from 124 days to 290 days, and the analyses revealed that, during this period within the patients, the isolates underwent several genetic and phenotypic changes. Considering the vast genetic diversity of cryptococcal isolates in sub-Saharan Africa, it was not surprising to find that the relapse isolates had acquired different genetic and ...
The main principles for the genetic pathophysiology of cryptococcosis will probably be consistent among all three varieties. In this chapter the author considers the yeasts to be different varieties or serotypes. Seven major areas are examined to support the potential molecular insights into this pathogenic yeast which will allow one to identify drug targets, define drug resistance mechanisms, and/or prepare mutants or fungal products for protective fungal vaccines. Initial molecular biology studies focused on distinguishing molecular strain differences with the use of karyotypes, repetitive elements, and eventually randomly amplified polymorphic DNAs, amplification fragment length polymorphisms, and PCR fingerprinting for strain genotyping. Cryptococcus neoformans has several well-characterized virulence phenotypes which have been approached in their understanding by both genetic and molecular tools. Experimental cryptococcosis in animal models has tended to be associated with large inocula or some
The recent efforts to characterize the hybrid strains of Cryptococcus neoformans has led to the identification of a cryptic population, here described as H strains, which includes hybrid strains with a double content of DNA but presenting a single mating type: Aa, Da, Aalpha, or Dalpha. A set of hypotheses can be formulated about the origin of these H strains: i) they might have lost or modified one mating type allele by a mutation event; ii) they might be homozygous originated from an incomplete mitotic event; iii) they might be homozygous originated from an incomplete meiotic event; iv) they might be homozygous originated from a post-meiotic event. To test these hypotheses we further investigated some H strains previously isolated and then we studied the F1 progeny originated from the mating between H99 (serotype A) and JEC20 (serotype D) reference strains. Fourteen clinical isolates were investigated. The double content of DNA was confirmed by flow cytometry and the presence of only one ...
The S. cerevisiae STE12 gene is a key component of two MAP kinase cascades involved in mating and filamentous/invasive growth (12)(13)(14)(15). Although STE12α shows sequence similarity with STE12 of S. cerevisiae, single copy or overexpression of STE12α cDNA in S. cerevisiae failed to complement the ste12 phenotypes, including the ability to mate and form pseudohyphae (data not shown). Recent identification of another C. neoformans MATα-specific gene, STE11α, which belongs to the same cascade, indicates an unusual arrangement of the MAP kinase cascade in C. neoformans (6). One of the intriguing findings in our study is that in contrast to the S. cerevisiae ste12 mutants, the C. neoformans ste12α disruptant was still able to mate, albeit with reduced frequency. The fact that STE12α is dispensable for mating further demonstrates the uniqueness of the mating pathway of C. neoformans.. Mating of C. neoformans is usually performed on V-8 juice agar and requires physical contact of cells from ...
Scientists have been studying the evolution of sex chromosomes for more than a century. In the 1960s, Japanese-American geneticist and evolutionary biologist Susumu Ohno proposed a theory in which the genes determining sex first arose at various spots scattered across the entire genome, but over time were "captured" on the sex chromosomes. In humans, those chromosomes go by the familiar X and Y; in birds, they are known as Z and W; in moss, they are called U and V.. Regardless of the name or species, Heitman contends that some universal principles could govern the evolution of all sex chromosomes. He and an international team of researchers focused on the last common ancestor of the human pathogen Cryptococcus neoformans and its nearest sibling species, a non-pathogen called Cryptococcus amylolentus.. In C. amylolentus, dozens of genes at two different locations on the chromosomes control whats called a tetrapolar, or four-part, mating system. At one location or locus known as P/R, genes ...
In Japan, most cases of cryptococcosis are caused by Cryptococcus neoformans(C. neoformans). Until now, only three cases which the infectious agent was Cryptococcus neoformans var. gattii(C. gattii)have been reported. As compared with cryptococcosis caused by C. neoformans, which is often observed in immunocompromised hosts, cryptococcosis caused by C. gattii occurs predominantly in immunocompetent hosts and is resistant to antifungal drugs. Here, we report a case of refractory cerebral cryptococcoma that was successfully treated by surgical resection of the lesions. A 33-year-old man with no medical history complained of headache, hearing disturbance, and irritability. Pulmonary CT showed a nodular lesion in the left lung. Cerebrospinal fluid examination with Indian ink indicated cryptococcal meningitis, and PCR confirmed infection with C. gattii. C. gattii is usually seen in the tropics and subtropics. Since this patient imported trees and soils from abroad to feed stag beetles, parasite or ...
Genetic analysis of oxygen-sensitive mutants of Cryptococcus neoformans revealed two loci (oxy1 and oxy2) linking hyperoxia sensitivity to production of melanin, a known virulence factor. Hyperoxia-sensitive strain 562 (oxy1 oxy2) is albino and avirulent. oxy2-defective strains lacking the oxy1 defect are melanin deficient but show normal hyperoxia resistance. Mutants defective at three additional mapped melanin loci fail to show hyperoxia sensitivity in the oxy1 background. Revertants of strain 562, which regain the ability to synthesize melanin by mutation at suppressor sites unlinked to oxy2, retain the oxygen sensitivity conferred by their oxy1 and oxy2 defects. These data identify the melanin gene oxy2 as unique in its association of hyperoxia resistance and melanization.
Deletion of the sex-determining gene SXI1α enhances the spread of mitochondrial introns in Cryptococcus neoformans Academic Article ...
Cryptococcus neoformans is a facultative intracellular opportunistic pathogen and the leading cause of fungal meningitis in humans. In the absence of a
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Torula histolytica Definition: Cryptococcus neoformans (formerly known as Torula histolytica) is an encapsulated yeast-like fungus found in (...)