Publications

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microtubules and actin cytoskeleton of potentially pathogenic basidiomycetous yeast as targets for antifungals.the cytoskeleton was investigated as a potential target for the inhibition of cell division in fellomyces fuzhouensis cbs 8243 related to cryptococcus neoformans.200919521073
cryptococcal granulomatous interstitial nephritis and dissemination in a patient with untreated lupus nephritis.infection is a significant cause of mortality and morbidity in systemic lupus erythematosus (sle). there are many reports of cryptococcal infection in patients with sle, on immunosuppression. however, untreated lupus with cryptococcal infection and dissemination is rare. cd4 lymphopaenia is not reported in such patients. we describe a patient with untreated sle to be having cryptococcal granulomatous interstitial nephritis and dissemination with cd4 lymphopaenia.200919525518
the fatty acid synthase of the basidiomycete omphalotus olearius is a single polypeptide.fatty acids are essential components of almost all biological membranes. additionally, they are important in energy storage, as second messengers during signal transduction, and in post-translational protein modification. de novo synthesis of fatty acids is essential for almost all organisms, and entails the iterative elongation of the growing fatty acid chain through a set of reactions conserved in all kingdoms. during our work on the biosynthesis of secondary metabolites, a 450-kda protein was ...200919526720
igm(+) memory b cell expression predicts hiv-associated cryptococcosis status.the role of b cells in resistance to cryptococcus neoformans disease (i.e., cryptococcosis) is unknown. given evidence that igm(+) memory b cells are required for immunity to other encapsulated pathogens, we hypothesized that these cells might contribute to resistance to cryptococcosis.200919527168
unusual presentations of nervous system infection by cryptococcus neoformans.nervous system infections by cryptococcus neoformans may occur not only in congenital or acquired immunodeficiency syndromes, but also in immunocompetent hosts. neurological manifestations of c. neoformans infection include meningitis and, less commonly, parenchymal cns granulomatous disease. this paper provides detailed clinical descriptions of highly unusual neurological manifestations of cryptococcal nervous system infections. medical records and diagnostic data including magnetic resonance i ...200919541406
remodeling of global transcription patterns of cryptococcus neoformans genes mediated by the stress-activated hog signaling pathways.the ability to sense and adapt to a hostile host environment is a crucial element for virulence of pathogenic fungi, including cryptococcus neoformans. these cellular responses are evoked by diverse signaling cascades, including the stress-activated hog pathway. despite previous analysis of central components of the hog pathway, its downstream signaling network is poorly characterized in c. neoformans. here we performed comparative transcriptome analysis with hog signaling mutants to explore str ...200919542307
production of extracellular polysaccharides by cap mutants of cryptococcus neoformans.the human pathogen cryptococcus neoformans causes meningoencephalitis. the polysaccharide capsule is one of the main virulence factors and consists of two distinct polysaccharides, glucuronoxylomannan (gxm) and galactoxylomannan (galxm). how capsular polysaccharides are synthesized, transported, and assembled is largely unknown. previously, it was shown that mutations in the cap10, cap59, cap60, and cap64 genes result in an acapsular phenotype. here, it is shown that these acapsular mutants do s ...200919542308
a microbial polysaccharide reduces the severity of rheumatoid arthritis by influencing th17 differentiation and proinflammatory cytokines production.rheumatoid arthritis (ra) is a chronic and debilitating autoimmune disease characterized by chronic joint inflammation with subsequent cartilage and bone destruction. ra is emerging as a model of il-17-driven autoimmune inflammatory disease. il-17 is a marker for th17 cells, with its master regulator being the retinoic acid receptor-related orphan receptor (rorgammat) regulated by stat3 signaling. glucuronoxylomannan (gxm), a polysaccharide representing the main component of the capsular materia ...200919542430
fungi pathogenic to humans: molecular bases of virulence of candida albicans, cryptococcus neoformans and aspergillus fumigatus.the frequency of severe systemic fungal diseases has increased in the last few decades. the clinical use of antibacterial drugs, immunosuppressive agents after organ transplantation, cancer chemotherapy, and advances in surgery are associated with increasing risk of fungal infections. opportunistic pathogens from the genera candida and aspergillus as well as pathogenic fungi from the genus cryptococcus can invade human organism and may lead to mucosal and skin infections or to deep-seated mycose ...200919543556
cerebellar cryptococcoma simulating metastatic neoplasm. 200919547825
inteins in pathogenic fungi: a phylogenetic tool and perspectives for therapeutic applications.inteins or 'internal proteins' are coding sequences that are transcribed and translated with flanking sequences (exteins). after translation, the inteins are excised by an autocatalytic process and the host protein assumes its normal conformation and develops its expected function. these parasitic genetic elements have been found in important, conserved proteins in all three domains of life. most of the eukaryotic inteins are present in the fungi kingdom and the prp8 intein is one of the most wi ...200919547879
fatal disseminated cryptococcus as the initial presentation of hiv infection in the era of highly active antiretroviral therapy.despite the availability of highly active antiretroviral treatment, many hiv-positive patients still present for the first time with a low cd4 count or an acquired immune deficiency syndrome (aids) defining illness. this may be due to patients' refusal to be tested for hiv, delay in seeking medical treatment, or the misdiagnosis of an aids-associated condition. we present a 39-year-old african american male with undiagnosed hiv, who died shortly after arrival to the emergency room. an autopsy wa ...200919486441
antifungal activity of tamoxifen: in vitro and in vivo activities and mechanistic characterization.tamoxifen (tam), an estrogen receptor antagonist used primarily to treat breast cancer, has well-recognized antifungal properties, but the activity of tam has not been fully characterized using standardized (i.e., clsi) in vitro susceptibility testing, nor has it been demonstrated in an in vivo model of fungal infection. in addition, its mechanism of action remains to be clearly defined at the molecular level. here, we report that tam displays in vitro activity (mic, 8 to 64 microg/ml) against p ...200919487443
cytokine signaling regulates the outcome of intracellular macrophage parasitism by cryptococcus neoformans.the pathogenic yeast cryptococcus neoformans and c. gattii commonly cause severe infections of the central nervous system in patients with impaired immunity but also increasingly in immunocompetent individuals. cryptococcus is phagocytosed by macrophages but can then survive and proliferate within the phagosomes of these infected host cells. moreover, cryptococcus is able to escape into the extracellular environment via a recently discovered nonlytic mechanism (termed expulsion or extrusion). al ...200919487474
most environmental isolates of cryptococcus neoformans var. grubii (serotype a) are not lethal for mice.most cases of cryptococcosis are caused by cryptococcus neoformans var. grubii (serotype a), which is widespread in the environment, where it is primarily associated with pigeon excreta. a number of molecular epidemiological studies indicate that many environmental and clinical isolates of serotype a are indistinguishable. however, the murine virulence of environmental strains of c. neoformans has not been thoroughly evaluated. we used the murine intranasal model of cryptococcosis to compare the ...200919487475
surface-associated plasminogen binding of cryptococcus neoformans promotes extracellular matrix invasion.the fungal pathogen cryptococcus neoformans is a leading cause of illness and death in persons with predisposing factors, including: malignancies, solid organ transplants, and corticosteroid use. c. neoformans is ubiquitous in the environment and enters into the lungs via inhalation, where it can disseminate through the bloodstream and penetrate the central nervous system (cns), resulting in a difficult to treat and often-fatal infection of the brain, called meningoencephalitis. plasminogen is a ...200919492051
differential activation of peritoneal cells by subcutaneous treatment of rats with cryptococcal antigens.previous studies in our laboratory have shown that the subcutaneous pretreatment of rats with heat-killed cells (hkc) of cryptococcus neoformans emulsified in complete freund adjuvant (cfa) promotes protective immunity against an intraperitoneal challenge with c. neoformans. in contrast, subcutaneous treatment with the capsular polysaccharide (psc) emulsified in cfa exacerbates the cryptococcal infection. the purpose of this study was to analyze the mechanisms involved in these phenomena. adhere ...200919494083
permethrin induces overexpression of multiple genes in aedes aegypti.using the polymerase chain reaction (pcr)-select subtractive cdna hybridization technique, 18 different genes were isolated from a permethrin-treated versus acetone-treated aedes aegypti subtractive library. quantitative pcr (qpcr) results showed that 8 of the 18 gene's transcriptional levels in permethrin-treated ae. aegypti were at least two-fold higher (ranging from 2.6 +/- 0.5 to 4.8 +/- 0.2) than that in acetone-treated ae. aegypti. these eight genes include three functionally known genes ( ...200919496430
carbonic anhydrase inhibitors. inhibition of the fungal beta-carbonic anhydrases from candida albicans and cryptococcus neoformans with boronic acids.inhibition of the beta-carbonic anhydrases (cas, ec 4.2.1.1) from the pathogenic fungi cryptococcus neoformans (can2) and candida albicans (nce103) with a series of aromatic, arylalkenyl- and arylalkylboronic acids was investigated. aromatic, 4-phenylsubstituted- and 2-naphthylboronic acids were the best can2 inhibitors, with inhibition constants in the range of 8.5-11.5microm, whereas arylalkenyl and aryalkylboronic acids showed k(i)s in the range of 428-3040microm. nce103 showed a similar inhi ...200919375309
fatty acid metabolism in the ectomycorrhizal fungus laccaria bicolor.here, the genome sequence of the ectomycorrhizal basidiomycete laccaria bicolorwas explored with the aim of constructing a genome-wide inventory of genes involved in fatty acid metabolism. sixty-three genes of the major pathways were annotated and validated by the detection of the corresponding transcripts. seventy-one per cent belonged to multigene families of up to five members. in the mycelium of l. bicolor, 19 different fatty acids were detected, including at low concentrations palmitvacceni ...200919383096
activity of contemporary antifungal agents, including the novel echinocandin anidulafungin, tested against candida spp., cryptococcus spp., and aspergillus spp.: report from the sentry antimicrobial surveillance program (2006 to 2007).results from the sentry international fungal surveillance program for 2006 to 2007 are presented. a total of 1,448 candida sp., 49 aspergillus fumigatus, and 33 cryptococcus neoformans isolates were obtained from infected sterile-site sources in patients on five continents. reference susceptibility was determined for anidulafungin, caspofungin, 5-flucytosine, fluconazole, itraconazole, posaconazole, voriconazole, and amphotericin b by clsi methods.200919386851
disseminated cryptococcosis in an hiv-negative patient. 200919389642
rapid etiological classification of meningitis by nmr spectroscopy based on metabolite profiles and host response.bacterial meningitis is an acute disease with high mortality that is reduced by early treatment. identification of the causative microorganism by culture is sensitive but slow. large volumes of cerebrospinal fluid (csf) are required to maximise sensitivity and establish a provisional diagnosis. we have utilised nuclear magnetic resonance (nmr) spectroscopy to rapidly characterise the biochemical profile of csf from normal rats and animals with pneumococcal or cryptococcal meningitis. use of a mi ...200919390697
protection by anti-beta-glucan antibodies is associated with restricted beta-1,3 glucan binding specificity and inhibition of fungal growth and adherence.anti-beta-glucan antibodies elicited by a laminarin-conjugate vaccine confer cross-protection to mice challenged with major fungal pathogens such as candida albicans, aspergillus fumigatus and cryptococcus neoformans. to gain insights into protective beta-glucan epitope(s) and protection mechanisms, we studied two anti-beta-glucan monoclonal antibodies (mab) with identical complementarity-determining regions but different isotypes (mab 2g8, igg2b and mab 1e12, igm). c. albicans, the most relevan ...200919399183
cryptococcosis of the upper genital tract.upper genital tract infection by cryptococcus neoformans has not previously been reported. we describe such a case, in order to alert clinicians to the existence of this rare infection. a 34-year-old woman with aids presented with chronic menorrhagia, fever, anemia, and thrombocytopenia. despite blood transfusions and hormonal therapy, her vaginal bleeding could not be controlled and she became hemodynamically unstable. total abdominal hysterectomy and bilateral salpingo-oophorectomy were perfor ...200919236159
evolutionarily conserved recognition and innate immunity to fungal pathogens by the scavenger receptors scarf1 and cd36.receptors involved in innate immunity to fungal pathogens have not been fully elucidated. we show that the caenorhabditis elegans receptors ced-1 and c03f11.3, and their mammalian orthologues, the scavenger receptors scarf1 and cd36, mediate host defense against two prototypic fungal pathogens, cryptococcus neoformans and candida albicans. ced-1 and c03f11.1 mediated antimicrobial peptide production and were necessary for nematode survival after c. neoformans infection. scarf1 and cd36 mediated ...200919237602
virulence in cryptococcus species.cryptococcus neoformans and cryptococcus gattii are the cause of life-threatening meningoencephalitis in immunocompromised and immunocompetent individuals respectively. the increasing incidence of cryptococcal infection as a result of the aids epidemic, the recent emergence of a hypervirulent cryptococcal strain in canada and the fact that mortality from cryptococcal disease remains high have stimulated intensive research into this organism. here we outline recent advances in our understanding o ...200919245939
management of severe community-acquired septic meningitis in adults: from emergency department to intensive care unit.to study the clinical features, diagnostic processes, timing of antibiotic administration and outcomes of patients with severe community-acquired septic meningitis at an emergency department (ed), who required intensive care unit (icu) admission.200919251546
antibody-mediated immobilization of cryptococcus neoformans promotes biofilm formation.most microbes, including the fungal pathogen cryptococcus neoformans, can grow as biofilms. biofilms confer upon microbes a range of characteristics, including an ability to colonize materials such as shunts and catheters and increased resistance to antibiotics. here, we provide evidence that coating surfaces with a monoclonal antibody to glucuronoxylomannan, the major component of the fungal capsular polysaccharide, immobilizes cryptococcal cells to a surface support and, subsequently, promotes ...200919251903
nasal cryptococcosis in two dogs in new zealand.two young, large-breed female dogs were presented with an acute onset of sneezing and nasal discharge. one patient had concurrent epistaxis and facial deformity.200919252544
inteins and introns within the prp8 -gene of four eupenicillium species.inteins are protein-intervening sequences that are translated with the host protein and can self-excise themselves post-translationally in an autocatalytic process. the flanking regions--called exteins--are then re-ligated with a new peptide bond, resulting in a mature host protein. previously, we have identified inteins in the highly conserved 3.2 region of the prp8 protein from species of the genus penicillium. these inteins are integrated at the same position as that which has recently been d ...200919253333
in contrast to anti-tumor activity, yt cell and primary nk cell cytotoxicity for cryptococcus neoformans bypasses lfa-1.nk cell cytotoxicity requires two positive signals for killing of tumors. activation receptors induce polarization of the microtubule organization center and degranulation, while leukocyte function-associated antigen (lfa)-1 is required for conjugate formation and actin polymerization and under some circumstances may be sufficient for nk cell cytotoxicity. although the receptor for direct killing of fungi is not known, cd18, the beta2 chain of lfa-1, binds components of the capsule and cell wall ...200919261694
the outcome of cryptococcus neoformans intracellular pathogenesis in human monocytes.cryptococcus neoformans is an encapsulated yeast that is a facultative intracellular pathogen. the interaction between macrophages and c. neoformans is critical for extrapulmonary dissemination of this pathogenic yeast. c. neoformans can either lyse macrophages or escape from within them through a process known as phagosomal extrusion. however, most studies of intracellular pathogenesis have been made with mouse cells and their relevance to human infection is uncertain. in this study we extended ...200919265539
cryptococcal cerebellitis after chemotherapy and autologous stem cell re-infusion in a patient with multiple myeloma. 200919267173
[cryptococcus neoformans meningoencephalitis in a patient treated with rituximab]. 200919268330
isolation and characterization of senescent cryptococcus neoformans and implications for phenotypic switching and pathogenesis in chronic cryptococcosis.although several virulence factors and associated genes have been identified, the mechanisms that allow cryptococcus neoformans to adapt during chronic infection and to persist in immunocompromised hosts remain poorly understood. characterization of senescent cells of c. neoformans demonstrated that these cells exhibit a significantly enlarged cell body and capsule but still cross the blood-brain barrier. c. neoformans cells with advanced generational age are also more resistant to phagocytosis ...200919411622
heteroresistance to fluconazole in cryptococcus neoformans is intrinsic and associated with virulence.in 1999, heteroresistance to triazoles was reported in cryptococcus neoformans strains isolated from an azole therapy failure case of cryptococcosis in an aids patient and in a diagnostic strain from a non-aids patient. in this study, we analyzed 130 strains of c. neoformans isolated from clinical and environmental sources before 1979, prior to the advent of triazoles, and 16 fluconazole (flc)-resistant strains isolated from aids patients undergoing flc maintenance therapy during 1990 to 2000. a ...200919414582
involvement of glycoreceptors in galactoxylomannan-induced t cell death.the major virulence factor of cryptococcus neoformans is its capsular polysaccharide, which is also released into tissues. the shed polysaccharide is composed of glucuronoxylomannan, galactoxylomannan (galxm), and mannoproteins. in a previous study, we demonstrated a direct interaction of purified soluble galxm with t cells that induced their apoptosis. in this study, we focus on the mechanisms involved in the apoptotic effect of galxm. in our experimental system, we analyzed the effect of galxm ...200919414751
synthesis, spectral, crystal and antimicrobial studies of biologically potent oxime ethers of nitrogen, oxygen and sulfur heterocycles.three series of oxime ethers viz, 2,6-diarylpiperidin-4-one o-benzyloximes 5a-o, 2,6-diaryltetrahydropyran-4-one o-benzyloximes 7a-e and 2,6-diaryltetrahydrothiopyran-4-one o-benzyloximes 11a-b and 12a-c were synthesized and stereochemistry is established by their spectral and single crystal analysis. a sar study has been carried out for the above oxime ethers against a panel of antibacterial (pseudomonas aeruginosa, staphylococcus aureus, salmonella typhi and escherichia coli) and antifungal ag ...200919419867
comparison of chemical compositions and antimicrobial activities of essential oils from three conifer trees; pinus densiflora, cryptomeria japonica, and chamaecyparis obtusa.the chemical compositions, and antibacterial and antifungal effects of essential oils extracted from three coniferous species, pinus densiflora, cryptomeria japonica, and chamaecyparis obtusa, were investigated. gas chromatography mass analysis of the essential oils revealed that the major components and the percentage of each essential oil were 16.66% beta-phellandrene and 14.85% alpha-pinene in p. densiflora; 31.45% kaur-16-ene and 11.06% sabinene in c. japonica; and 18.75% bicyclo [2, 2, 1] h ...200919420996
uncommon presentation of intracranial cryptococcal infection mimicking tuberculous infection in two immunocompetent patients.cryptococcal infection of the brain is commonly seen in immunocompromised patients but rarely considered as the differential diagnosis in immunocompetent patients. we present two cases of cryptococcosis involving the brain in immunocompetent patients, which strongly mimicked tuberculous infection in both conventional as well as advanced magnetic resonance (mr) imaging, and the disease was only confirmed after histopathological/cerebrospinal fluid serological study. one patient was a 52-year-old ...200919421667
sequestration of active cryptococcus neoformans infection in the parathyroid gland despite prolonged therapy in a renal transplant recipient.disseminated cryptococcal infection occurs mainly in the immunocompromised host, particularly in those with impaired cellular immunity. the treatment outcome depends not only on the duration and choice of antifungal therapy, but also on the activity of the organism to persist in different parts of the body despite therapy. we present a case of persistence of cryptococcal infection in the parathyroid gland in a kidney transplant recipient. a 38-year-old male renal transplant recipient diagnosed t ...200919422668
cryptococcal disease presenting as necrotizing cellulitis in transplant recipients.disseminated cryptococcosis uncommonly presents with skin lesions in immunocompromised hosts. necrotizing fasciitis, necrotizing vasculitis, myositis, or necrotizing soft tissue infection are even more rare presentations. we report 3 cases of cryptococcal necrotizing soft tissue infection, 2 in renal transplant patients, and 1 in a heart transplant patient, and discuss similar cases from the literature. cryptococcus neoformans should be considered in the differential diagnosis of cellulitis or n ...200919422669
cryptococcus neoformans fatal sepsis in a chronic lymphocytic leukemia patient treated with alemtuzumab: case report and review of the literature.cryptococcosis is a disseminated fungal disease typically associated with immunosuppression and characterized by high mortality rates. cryptococcus neoformans has been reported to be isolated from blood cultures in around 20% of patients with cryptococcosis, and cryptococcemia has been correlated with poor prognosis. we report a case of fatal c. neoformans fungemia in a neutropenic patient with a history of chronic lymphocytic leukemia treated with alemtuzumab. the patient presented with loss of ...200919423476
interaction of triosephosphate isomerase from the cell surface of staphylococcus aureus and alpha-(1->3)-mannooligosaccharides derived from glucuronoxylomannan of cryptococcus neoformans.the glycolytic enzyme triosephosphate isomerase (tpi; ec 5.3.1.1) of staphylococcus aureus is a candidate adhesion molecule for the interaction between the bacterium and the fungal pathogen cryptococcus neoformans. tpi may recognize the mannan backbone of glucuronoxylomannan (gxm) of c. neoformans. we purified tpi from extracts of s. aureus surface proteins to investigate its binding by surface plasmon resonance analysis. the immobilized tpi reacted with gxm in a dose-dependent manner. furthermo ...200919423633
[an hiv positive man with skin ulcers in the face. cryptococcus]. 200919425329
the capsule of the fungal pathogen cryptococcus neoformans.the capsule of the fungal pathogen cryptococcus neoformans has been studied extensively in recent decades and a large body of information is now available to the scientific community. well-known aspects of the capsule include its structure, antigenic properties and its function as a virulence factor. the capsule is composed primarily of two polysaccharides, glucuronoxylomannan (gxm) and galactoxylomannan (galxm), in addition to a smaller proportion of mannoproteins (mps). most of the studies on ...200919426855
antifungal alkaloids from the fresh rattan stem of fibraurea recisa pierre.the rattan stem of fibraurea recisa pierre. is known as an ethno-remedy commonly used for the treatment of various skin diseases by the minority yao, zhuang and miao in yunnan province of china. the present study was designated to evaluate its antifungal activity, and to root out the antifungal substances from this ethical herb.200919429331
antimicrobial activity of acacia mellifera extracts and lupane triterpenes.acacia mellifera (vahl) benth (leguminosae) is a subtropical medicinal plant that is widely used in traditional african medicines against various diseases such as pneumonia and malaria.200919429353
antifungal activity of itraconazole and voriconazole against clinical isolates obtained from animals with mycoses.animal mycosis, particularly deep mycosis, is one of the most challenging conditions encountered by veterinarians. pathogens causing mycotic infections in animals include fungi such as cryptococcus neoformans, candida spp., and aspergillus spp. the antifungal drugs used for the treatment of deep mycoses in animals as well as humans are polyenes and azoles. however, the sensitivity of clinical isolates obtained from animals toward these drugs has rarely been assayed. in this study, the antifungal ...200919430183
growth inhibitory action of ebselen on fluconazole-resistant candida albicans: role of the plasma membrane h+-atpase.pma1 is a yeast gene that codes for the plasma membrane h(+)-atpase, a protein commonly referred to as pma1p. ebselen (2-phenyl-1,2-benzisoselenazol-3(2h)-one) is a synthetic selenium-containing compound that has recently been shown to display antimicrobial activity owing to its ability to inhibit pma1p. ebselen is able to block the activity of pma1p not only in opportunistic pathogens such as cryptococcus neoformans and candida albicans but also in nonpathogenic yeasts such as saccharomyces cer ...200919432523
bulky 1,4-benzoxazine derivatives with antifungal activity.for many years the development of new azole antifungals has been quite empirically based. more recently, the publication of the crystal structure of cyp51 of mycobacterium tuberculosis (mt-cyp51) provided new opportunities to rationalize the knowledge about antifungal action of this class of compounds. recent studies reported that a 'channel 2 opened' conformation of the enzyme could better explain the interaction with ketoconazole (ktz)-like drugs. conformational changes were made on our model ...200919433362
intraocular cryptococcoma. 200919433726
chromosomal rearrangements between serotype a and d strains in cryptococcus neoformans.cryptococcus neoformans is a major human pathogenic fungus that can cause meningoencephalitis in immunocompromised hosts. it contains two divergent varieties, var. grubii (serotype a) and var. neoformans (serotype d), as well as hybrids (serotype ad) between these two varieties. in this study, we investigated the extent of chromosomal rearrangements between the two varieties, estimated the effects of chromosomal rearrangements on recombination frequencies, and surveyed the potential polymorphism ...200919436753
antimicrobial and brine shrimp toxicity of some plants used in traditional medicine in bukoba district, north-western tanzania.herbal medicines constitute a potentially important resource for new and safe drugs for the management of microbial infections and other diseases. in this study, dichloromethane, ethylacetate and ethanol extracts of canarium schweinfurthii engl., dissotis brazzae cong., iboza urticifolia (bak) e.a.bruce, isoglosa lacteal lindau, strombosia scheffleri engl., and whitfieldia elongate t. anders were tested for antimicrobial activity and brine shrimp toxicity. the objective was to validate claims th ...200919445101
broad-spectrum antimicrobial peptides by rational combinatorial design and high-throughput screening: the importance of interfacial activity.we recently described 10 peptides selected from a 16,384-member combinatorial library based on their ability to permeabilize synthetic lipid vesicles in vitro. these peptides did not share a common sequence motif, length, or net charge; nonetheless, they shared a mechanism of action that is similar to the natural membrane permeabilizing antimicrobial peptides (amp). to characterize the selected peptides and to compare the activity of amps in vivo and in vitro, we report on the biological activit ...200919445503
chemical composition, toxicity and larvicidal and antifungal activities of persea americana (avocado) seed extracts.the present study had the aim of testing the hexane and methanol extracts of avocado seeds, in order to determine their toxicity towards artemia salina, evaluate their larvicidal activity towards aedes aegypti and investigate their in vitro antifungal potential against strains of candida spp, cryptococcus neoformans and malassezia pachydermatis through the microdilution technique. in toxicity tests on artemia salina, the hexane and methanol extracts from avocado seeds showed lc50 values of 2.37 ...200919448924
an unusual organelle in cryptococcus neoformans links luminal ph and capsule biosynthesis.cryptococcus neoformans is a basidiomycete that causes deadly infections in the immunocompromised. we previously generated a secretion mutant in this fungus by introducing a mutation in the sav1 gene, which encodes a homolog of the sec4/rab8 subfamily gtpases. under restrictive conditions there are two notable morphological changes in the sav1 mutant: accumulation of post-golgi vesicles and the appearance of an unusual organelle, which we term the sav1 body (sb). the sb is an electron-transparen ...200919450701
carbonic anhydrase inhibitors. inhibition and homology modeling studies of the fungal beta-carbonic anhydrase from candida albicans with sulfonamides.the beta-carbonic anhydrase (ca, ec 4.2.1.1) from the fungal pathogen candida albicans (nce103) is involved in a co(2) sensing pathway critical for the pathogen life cycle and amenable to drug design studies. herein we report an inhibition study of nce103 with a library of sulfonamides and one sulfamate, showing that nce103, similarly to the related enzyme from cryptococcus neoformans can2, is inhibited by these compounds with k(i)s in the range of 132 nm-7.6 microm. the best nce103 inhibitors w ...200919450983
elucidating the pathogenesis of spores from the human fungal pathogen cryptococcus neoformans.cryptococcus neoformans was first described as a human fungal pathogen more than a century ago. one aspect of the c. neoformans infectious life cycle that has been the subject of earnest debate is whether the spores are pathogenic. despite much speculation, no direct evidence has been presented to resolve this outstanding question. we present evidence that c. neoformans spores are pathogenic in a mouse intranasal inhalation model of infection. in addition, we provide mechanistic insights into sp ...200919451235
surfactant protein d increases phagocytosis of hypocapsular cryptococcus neoformans by murine macrophages and enhances fungal survival.cryptococcus neoformans is a facultative intracellular opportunistic pathogen and the leading cause of fungal meningitis in humans. in the absence of a protective cellular immune response, the inhalation of c. neoformans cells or spores results in pulmonary infection. c. neoformans cells produce a polysaccharide capsule composed predominantly of glucuronoxylomannan, which constitutes approximately 90% of the capsular material. in the lungs, surfactant protein a (sp-a) and sp-d contribute to immu ...200919451250
successful treatment of cryptococcal meningitis with a combination of liposomal amphotericin b, flucytosine and posaconazole: two case reports.cryptococcus neoformans cns infection frequently affects hiv-infected patients and is often lethal, despite antifungal therapy. the most recent treatment guidelines for cryptococcal meningitis recommend therapy with lyposomal amphotericin b and possible association with flucitosine. however, clinical response rates in hiv-infected patients are not satisfactory, with a persistent high mortality rate and long term therapy is affected by a high risk of major side effects. posaconazole, the latest b ...200919454515
a copper-responsive factor gene cuf1 is required for copper induction of laccase in cryptococcus neoformans.the multicopper laccase is a major virulence factor in cryptococcus neoformans. its expression regulation is complex. we presented molecular evidence to show that laccase expression was induced by high concentrations of exogenous copper. melanin production and laccase enzymatic activity increased dramatically in response to the addition of copper to the media. reverse transcription-pcr amplification of the laccase gene lac1 mrna revealed that the induction occurred at the transcriptional level, ...200919459959
cryptococcus neoformans: morphogenesis, infection, and evolution.cryptococcus neoformans is the major causative agent of fungal meningoencephalitis in both immunocompromised and immunocompetent individuals. during infection, this fungus is observed in the yeast form and is only occasionally seen as the pseudohyphal or hyphal form (filamentous forms). early studies suggested that phase transition of c. neoformans from a multi-cellular filamentous form to the unicellular yeast form might be essential for the survival of this fungus in mammalian hosts. however, ...200919460306
consensus multi-locus sequence typing scheme for cryptococcus neoformans and cryptococcus gattii.this communication describes the consensus multi-locus typing scheme established by the cryptococcal working group i (genotyping of cryptococcus neoformans and c. gattii) of the international society for human and animal mycology (isham) using seven unlinked genetic loci for global strain genotyping. these genetic loci include the housekeeping genes cap59,gpd1, lac1, plb1, sod1, ura5 and the igs1 region. allele and sequence type information are accessible at http://www.mlst.net/ .200919462334
novel antifungal agents, targets or therapeutic strategies for the treatment of invasive fungal diseases: a review of the literature (2005-2009).the incidence and prevalence of serious mycoses continues to be a public health problem. despite aggressive treatment with new or more established licensed antifungal agents, these infections are an important cause of morbidity and mortality, especially in immunocompromised patients.200919463273
antimicrobial activities of methanol extract and compounds from stem bark of vismia rubescens.the plant, vismia rubescens (guttiferae) is popularly used in cameroon and in several parts of africa as febrifugal and for the treatment of various microbial infections (skin diseases, diarrhoea and venereal diseases).200919464353
the common cryptococcus neoformans glucuronoxylomannan m2 motif elicits non-protective antibodies.the cryptococcus neoformans capsular glucuronoxylomannan (gxm) is a potential vaccine antigen that can elicit protective and non-protective antibodies. in an attempt to focus the immune response on a single antigenic component, a heptasaccharide oligosaccharide representing the major structural motif (m2) of the most common clinical isolate was synthesized and conjugated to human serum albumin (hsa). monoclonal antibodies (mabs) generated from mice immunized with m2-hsa produced the characterist ...200919464529
lipophilic dye staining of cryptococcus neoformans extracellular vesicles and capsule.cryptococcus neoformans is an encapsulated yeast that causes systemic mycosis in immunosuppressed individuals. recent studies have determined that this fungus produces vesicles that are released to the extracellular environment both in vivo and in vitro. these vesicles contain assorted cargo that includes several molecules associated with virulence and implicated in host-pathogen interactions, such as capsular polysaccharides, laccase, urease, and other proteins. to date, visualization of extrac ...200919465562
three-dimensional model of lanosterol 14 alpha-demethylase from cryptococcus neoformans: active-site characterization and insights into azole binding.cryptococcus neoformans is one of the most important causes of life-threatening fungal infections in immunocompromised patients. lanosterol 14 alpha-demethylase (cyp51) is the target of azole antifungal agents. this study describes, for the first time, the 3-dimensional model of cyp51 from cryptococcus neoformans (cncyp51). the model was further refined by energy minimization and molecular-dynamics simulations. the active site of cncyp51 was well characterized by multiple-copy simultaneous-searc ...200919470512
[study of mycological examination methods in clinical laboratories--specimen pretreatment and isolation].we performed a comparative study of the effects of centrifugation, large amounts of inoculum and incubation temperature with regard to recovery of candida albicans, cryptococcus neoformans and aspergillus fumigatus from fungal suspensions in order to identify optimal processing methods for mycological examination of clinical specimens. the number of fungal colonies, except for candida spp., isolated from respiratory specimens, and the duration of incubation needed to isolate pathogenic fungi fro ...200919942795
cryptococcus neoformans meningitis in a diabetic patient--the perils of an overzealous immune response: a case report.uncontrolled diabetics are prone to infections due to numerous factors as the glucose-rich blood serves as an excellent media for growth. cryptococcus neoformans is an opportunistic fungus that is an important cause of cns infections among immunocompromised patients, but it has only sporadically been reported in non-hiv-positive persons. the presence of elevated pro-inflammatory cytokines and abnormalities in numerous systemic indicators of inflammation in diabetics makes it conceivable that dia ...200919946453
disseminated cryptococcosis with meningitis, peritonitis, and cryptococcemia in a hiv-negative patient with cirrhosis: a case report.cryptococcus neoformans is an encapsulated yeast that causes serious infections in immunocompromised populations. the majority of cases occur in hiv-infected individuals. disseminated disease is uncommon, and very rarely includes peritonitis.200919946481
variables that influence hiv-1 cerebrospinal fluid viral load in cryptococcal meningitis: a linear regression analysis.abstract:200919906308
cryptococcal meningitis with an antecedent cutaneous cryptococcal lesion.cutaneous cryptococcosis, caused by an encapsulated yeast, cryptococcus neoformans, is generally associated with concomitant systemic infection. here we report a case of primary cutaneous cryptococcosis with spread to central nervous system in an hiv seronegative young boy. in the present case, a 17-year-old boy who was suffering from a non-healing ulcer on his right great toe for 5 months, presented with the signs and symptoms of meningitis. cryptococcus neoformans var. gattii was isolated from ...200919930999
accumulation of cd11b+ lung dendritic cells in response to fungal infection results from the ccr2-mediated recruitment and differentiation of ly-6chigh monocytes.pulmonary clearance of the encapsulated yeast cryptococcus neoformans is associated with the ccr2-mediated accumulation of lung dendritic cells (dc) and the development of a t1 adaptive immune response. the objective of this study was to identify the circulating dc precursor(s) responsible for this large increase in lung dc numbers. an established murine model was used to evaluate putative dc precursors in the blood, bone marrow, and lungs of ccr2(+/+) mice and ccr2(-/-) mice throughout a time c ...200919933856
chapter 3--pulmonary cryptococcosis.cryptococcosis is a systemic mycosis caused by two species of the encapsulated basidiomycetes, cryptococcus neoformans and c. gattii, which, respectively, cause infection in immunocompromised individuals and in immunologically normal hosts. patients with t-cell deficiencies are more susceptible to this infection. the spectrum of the disease ranges from asymptomatic pulmonary lesions to disseminated infection with meningoencephalitis. the medical relevance of cryptococcosis increased dramatically ...200920011850
candida albicans, cryptococcus neoformans or aspergillus fumigatus induces an antifungal activity in mouse serum, which is different from transferrin.it has been reported that administration of candida albicans into mouse induces an antifungal activity in serum, which has been identified as transferrin. in the present study, we show that not only c. albicans, but also other fungus such as cryptococcus neoformans or aspergillus fumigatus similarly can induce an antifungal activity in mouse serum. this antifungal activity was inhibited by the addition of ferrous ion, indicating that the growth inhibition of c. albicans was due to deficiency of ...200919959896
[immune reconstitution inflammatory syndrome and treatment of hiv infection].haart (highly active antiretroviral therapy) may trigger a condition known as iris (immune reconstitution inflammatory syndrome); i.e. a paradoxical reaction to latent infections associated with reconstitution of the immune system. the article provides an overview of the syndrome and discusses diagnosis, risk factors and management.200919997137
pathology in practice. systemic cryptococcosis caused by c. neoformans and concomitant severe pulmonary aelurostrongylosis. 200920001772
four-week fluconazole treatment is recommended for localized granulomatous cryptococcal prostatitis in patients with liver cirrhosis. 200920002845
management of endogenous cryptococcal endophthalmitis with voriconazole. 200920051999
necrotizing fasciitis due to cryptococcus neoformans in a diabetic patient with chronic renal insufficiency. 200920055888
cryptococcus neoformans site-2 protease is required for virulence and survival in the presence of azole drugs.in the human fungal pathogen cryptococcus neoformans, the srebp orthologue sre1 is important for adaptation and growth in nutrient-limiting host tissues. in this study, we characterize the c. neoformans serotype a sre1 and its activating protease, stp1. we demonstrate that stp1 is a functionally conserved orthologue of the mammalian site-2 protease and that stp1 cleaves sre1 within its predicted first transmembrane segment. gene expression analysis revealed that stp1 is required for both sre1-de ...200919818023
cryptococcus gattii: an emerging cause of fungal disease in north america.during the latter half of the twentieth century, fungal pathogens such as cryptococcus neoformans were increasingly recognized as a significant threat to the health of immune compromised populations throughout the world. until recently, the closely related species c. gattii was considered to be a low-level endemic pathogen that was confined to tropical regions such as australia. since 1999, c. gattii has emerged in the pacific northwest region of north america and has been responsible for a larg ...200919503836
cryptococcal disease in patients with or without human immunodeficiency virus: clinical presentation and monitoring of serum cryptococcal antigen titers.cryptococcus neoformans is an encapsulated pathogenic yeast that causes a wide range of clinical manifestations. the serum cryptococcal latex agglutination test is a simple, rapid, and reliable diagnostic test for cryptococcosis. this study was performed to assess the clinical relevance of serum cryptococcal antigen (crag) titer in patients with cryptococcosis with or without human immunodeficiency virus (hiv).200919812855
puupehanol, a sesquiterpene-dihydroquinone derivative from the marine sponge hyrtios sp.puupehanol (1), a new sesquiterpene-dihydroquinone derivative, was isolated from the marine sponge hyrtios sp., along with the known compounds puupehenone (2) and chloropuupehenone (3) that are responsible for the antifungal activity observed in the extract. the structure of 1 was established as (20r,21r)-21-hydroxy-20,21-dihydropuupehenone by extensive spectroscopic and computational methods. compound 2 exhibited potent activity against cryptococcus neoformans and candida krusei with mfcs of 1. ...200919783432
physico-chemical evaluation of rationally designed melanins as novel nature-inspired radioprotectors.melanin, a high-molecular weight pigment that is ubiquitous in nature, protects melanized microorganisms against high doses of ionizing radiation. however, the physics of melanin interaction with ionizing radiation is unknown.200919789711
activity of mgcd290, a hos2 histone deacetylase inhibitor, in combination with azole antifungals against opportunistic fungal pathogens.we report on the in vitro activity of the hos2 fungal histone deacetylase (hdac) inhibitor mgcd290 (methylgene, inc.) in combination with azoles against azole-resistant yeasts and molds. susceptibility testing was performed by the clsi m27-a3 and m38-a2 broth microdilution methods. testing of the combinations (mgcd290 in combination with fluconazole, posaconazole, or voriconazole) was performed by the checkerboard method. the fractional inhibitory concentrations were determined and were defined ...200919794038
identification of cryptococcus gattii by use of l-canavanine glycine bromothymol blue medium and dna sequencing.cryptococcus neoformans and cryptococcus gattii are closely related pathogenic fungi. cryptococcus neoformans is ecologically widespread and affects primarily immunocompromised patients, while c. gattii is traditionally found in tropical climates and has been reported to cause disease in immunocompetent patients. l-canavanine glycine bromothymol blue (cgb) agar can be used to differentiate c. neoformans and c. gattii, but there are few reports of its performance in routine clinical practice. gro ...200919794048
[mating types, sexual reproduction and ploidy in fungi: effects on virulence].sexual reproduction provides natural selection and adaptation of the organisms to environmental conditions by allowing benefical mutations to spread and by diluting deleterious mutations. in recent years new findings which indicate the role of sexual reproduction in fungal pathogenicity, have been obtained. however, the pathogenic fungi limit their sexual cycles to generate clonal populations instead of recombinants, to enable themselves to adapt to the new conditions in the environment and in t ...200919795629
regulatory diversity of tup1 in cryptococcus neoformans.cryptococcus neoformans serotype a strains, the major cause of cryptococcosis, are distributed worldwide, while serotype d strains are more concentrated in central europe. we have previously shown that deletion of the global regulator tup1 in serotype d isolates results in a novel peptide-mediated, density-dependent growth phenotype that mimics quorum sensing and is not known to exist in other fungi. unlike for tup1delta strains of serotype d, the density-dependent growth phenotype was found to ...200919820119
growth strategy of the pathogenic yeast cryptococcus neoformans submerged culture under different cultivation formats.growth patterns of cryptococcus neoformans submerged culture in different culture volumes, intensity of agitation and types of sealing were evaluated to better understand the physiological role of hypoxia response in this yeast. when low intensity agitation was set at high culture volumes and air exchange between the cultivation vessel and external environment was not abolished completely, the cells proliferated slowly but steadily. on the other hand, when the intensity of agitation was high but ...200919826923
peculiar clusters of daughter cells observed in cryptococcus neoformans grown in sealed microtiter plates.cryptococcus neoformans was grown in 96-well microtiter plates sealed by foil which is less than 0.01 % permeable to oxygen. on day 14 of the cultivation, we observed peculiar clusters of small droplike daughter cells arranged around < or = 4 % of mother cells. the fact that most of the other cells had died indicates that few cells had been able to survive hypoxic conditions and escape the cell-cycle arrest. however, their daughters were unable to separate from them and to continue their prolife ...200919826927
composition and anti-fungal activity of the essential oil from cameroonian vitex rivularis gürke.the chemical composition of the essential oils obtained by hydrodistillation from the aerial parts of two populations of vitex rivularis (subgenus vitex) collected during the flowering phase of the plants was investigated by gas chromatography and gas chromatography/mass spectroscopy. sesquiterpene hydrocarbons were the main group in both samples, the main compound being germacrene d. this composition is markedly different from that of the other african species, with the exception of vitex ferru ...200919844822
hypoxia sensing in cryptococcus neoformans: biofilm-like adaptation for dormancy?cryptococcus neoformans is an obligate aerobic pathogenic yeast causing lung infection typically followed by spread to the central nervous system. during pathogenesis, it relies on well-established virulence factors. this review focuses on the emerging role of cryptococcal adaptation to hypoxia in pathogenesis.200919851430
an efficient gene-disruption method in cryptococcus neoformans by double-joint pcr with nat-split markers.targeted gene disruption via biolistic transformation and homologous recombination is a method widely used to identify and investigate the function of genes in cryptococcus neoformans that causes fatal fungal meningitis if not timely treated. currently, most laboratories employ the overlap-pcr method to generate a gene-disruption cassette with dominant selectable markers, such as nourseothricin acetyltransferase (nat). however, the conventional overlap-pcr method is often found to be inefficient ...200919852932
[regulations diversity of fungal copper homeostasis--a review].copper is an essential trace element in all organisms and serves as a catalytic cofactor for many biological processes in cells. yet excess cuprous and cupric forms can be high toxic to the cells. thus cells must have developed diverse mechanisms to control the uptake and distribution of copper. much are known about the copper metabolism in saccharomyces cerevisiae and a few other fungi. in this review, we focus on the recent research in copper uptake, transport and distribution in model organis ...200919873745
regulating the t-cell immune response toward the h99 strain of cryptococcus neoformans. 200919875503
our current understanding of fungal biofilms.fungal biofilms are an escalating clinical problem associated with significant rates of mortality. candida albicans is the most notorious of all fungal biofilm formers. however, non-candida species, yeasts such as cryptococcus neoformans, and filamentous moulds such as aspergillus fumigatus, have been shown to be implicated in biofilm-associated infections. fungal biofilms have distinct developmental phases, including adhesion, colonisation, maturation and dispersal, which are governed by comple ...200919863383
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