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repression of proteases and hsp90 chaperone expression induced by an antiretroviral in virulent environmental strains of cryptococcus neoformans.this study evaluated the effect of the antiretroviral ritonavir on protease secretion in different strains of cryptococcus neoformans isolated from the environment and investigated the expression of heat shock protein (hsp90), classically described virulence factors in other yeast in the presence of the same antiretroviral. the presence of the enzyme was detected by the formation of a degradation of the halo around the colonies. the results were classified as follows: level 1 (without proteases) ...201727909750
fungal glycolipid hydrolase inhibitors and their effect on cryptococcus neoformans.pathogenic fungi kill an estimated 1.3 million people each year. this number is predicted to rise as drug resistance spreads, thus antifungal drugs with novel modes of action are urgently required. fungal endoglycoceramidase-related proteins 1 and 2 (egcrp-1 and -2), which hydrolyse glucosylceramide and ergosteryl β-glucoside, respectively, are important for fungal cell growth and have been identified as potential targets for drug development. a library of iminosugar derivatives was screened aga ...201727905163
de novo pyrimidine biosynthesis connects cell integrity to amphotericin b susceptibility in cryptococcus neoformans.the use of amphotericin b (amb) in conjunction with 5-fluorocytosine (5-fc) is known to be the optimal therapy for treating cryptococcosis, but the mechanism by which 5-fc synergizes with amb is unknown. in this study, we generated a cryptococcus neoformans ura1δ mutant lacking dihydroorotate dehydrogenase (dhodh), which demonstrated temperature-sensitive growth due to a defect in cell integrity and sensitivity to cell wall-damaging agents. in addition, sensitivity to amb was greatly increased. ...201727904878
microbiology of processed edible insect products - results of a preliminary survey.little is known of the microbiology of processed insect products. the present survey analysed a total of n=38 samples of deep-fried and spiced (acheta domesticus, locusta migratoria, and omphisa fuscidentalis), cooked in soy sauce ("tsukudani"; oxya yezoensis, vespula flaviceps, and bombyx mori), dried (a. domesticus, l. migatoria, alphitobius diaperinus, tenebrio molitor, b. mori, hermetia illucens, and musca domestica), powdered (h. illucens, t. molitor) and other (incl. deep-frozen b. mori an ...201727903420
chemical and functional properties of metal chelators that mobilize copper to elicit fungal killing of cryptococcus neoformans.a panel of iron (fe) and copper (cu) chelators was screened for growth inhibitory activity against the fungal pathogen cryptococcus neoformans. select bidentate metal-binding ligands containing mixed o,s or o,n donor atoms were identified as agents that induce cell killing in a cu-dependent manner. conversely, structurally similar ligands with o,o donor atoms did not inhibit c. neoformans growth regardless of cu status. studies of cu(ii) and cu(i) binding affinity, lipophilicity, and growth reco ...201727853789
disseminated cryptococcosis in a 63-year-old patient with multiple sclerosis treated with fingolimod.we herein report the case of a 63-year-old man who presented with a 3-month history of a cutaneous nodular lesion of his jaw, low grade fever, lethargy and progressive cognitive impairment. he had a 30-year history of multiple sclerosis and had been treated with fingolimod for the previous 2 years. laboratory data revealed cd4 lymphocytopenia and a tissue culture of the skin nodule was positive for cryptococcus neoformans. cerebrospinal fluid and serum cryptococcal antigen tests were also positi ...201727853088
prenylated flavonoids from the stems and roots of tripterygium wilfordii.phytochemical investigation on the stems and roots of tripterygium wilfordii led to the isolation and characterization of three new prenylated flavanones, tripteryols a-c (1-3), along with (±)-5,4'-dihydroxy-2'-methoxy-6',6″-dimethypyraro-(2″,3″:7,8)-6-methyflavanone (4), and ((2s)-5,7,4'-trihydroxy-2'-methoxy-8,5'-di(3-methyl-2-butenyl)-6-methylflavanone (5). structures of the compounds 1-5 were elucidated using spectroscopic techniques, such as uv, ir, nmr (1d and 2d), and hresi-ms. tripteryol ...201728389278
elucidation of the calcineurin-crz1 stress response transcriptional network in the human fungal pathogen cryptococcus neoformans.calcineurin is a highly conserved ca2+/calmodulin-dependent serine/threonine-specific protein phosphatase that orchestrates cellular ca2+ signaling responses. in cryptococcus neoformans, calcineurin is activated by multiple stresses including high temperature, and is essential for stress adaptation and virulence. the transcription factor crz1 is a major calcineurin effector in saccharomyces cerevisiae and other fungi. calcineurin dephosphorylates crz1, thereby enabling crz1 nuclear translocation ...201728376087
synthesis, stability and mechanistic studies of potent anticryptococcal hexapeptides.the growing incidents of cryptococcosis in immuno-compromised patients have created a need for novel drug therapies capable of eradicating the disease. the peptide-based drug therapy offers many advantages over the traditional therapeutic agents, which has been exploited in the present study by synthesizing a series of hexapeptides that exhibits promising activity against a panel of gram-negative and gram-positive bacteria and various pathogenic fungal strains; the most exemplary activity was ob ...201728363154
atypical presentation of cryptococcus neoformans in a koala (phascolarctos cinereus): a magnetic resonance imaging and computed tomography study.cryptococcosis is a worldwide and potentially fatal mycosis documented in wild and captive koalas ( phascolarctos cinereus ) caused by cryptococcus neoformans . though mainly a subclinical disease, when the nasal cavity is affected, epistaxis, mucopurulent nasal discharge, dyspnea, and facial distortion may occur. this report describes a case of cryptococcosis in a koala where unilateral exophthalmos was the only evident clinical sign and magnetic resonance imaging and computed tomography findin ...201728363053
a rare diagnosis: recognizing and managing fungal tenosynovitis of the hand and upper extremity.fungal infections involving the tenosynovium of the upper extremity are uncommon and are often misdiagnosed. this study evaluates the epidemiology, diagnosis, treatment, and outcomes of patients with fungal tenosynovitis of the upper extremity over a 20-year period.201728011032
infective capacity of cryptococcus neoformans and cryptococcus gattii in a human astrocytoma cell line.pathogenesis of cryptococcosis in the central nervous system (cns) is a topic of ongoing research, including the mechanisms by which this fungus invades and infects the brain. astrocytes, the most common cns cells, play a fundamental role in the local immune response. astrocytes might participate in cryptococcosis either as a host or by responding to fungal antigens. to determine the infectivity of cryptococcus neoformans var. grubii and cryptococcus gattii in a human astrocytoma cell line and t ...201728338245
molecular epidemiology of cryptococcal genotype vnic/st5 in siriraj hospital, thailand.despite the strong association between cryptococcus neoformans infection and the human immunodeficiency virus (hiv) status of patients globally, most cryptococcosis cases in far east asia occur in non-hiv individuals. molecular epidemiological studies, using multilocus sequence typing (mlst), have shown that more than 95% of cryptococcal strains belong to a specific subtype of vni. however, this association has never been specifically examined in other parts of asia. therefore, in this study, we ...201728323835
anti-cryptococcal activity of ethanol crude extract and hexane fraction from ocimum basilicum var. maria bonita: mechanisms of action and synergism with amphotericin b and ocimum basilicum essential oil.ocimum basilicum l. (lamiaceae) has been used in folk medicine to treat headaches, kidney disorders, and intestinal worms.201728317465
screening of invasive fungal infections by a real-time panfungal (pan-acf) polymerase chain reaction assay in patients with haematological malignancy.invasive fungal infection (ifi) is a fatal infection in haematology patients. there is an urgent need for reliable screening methods facilitating timely diagnosis and treatment. a real-time panfungal polymerase chain reaction (pcr) assay based on taqman technology targeting 18s ribosomal rna gene was used to screen whole blood specimen obtained from series of haematology malignancy patients for ifis.201728303817
disseminated cryptococcosis manifested as a single tumor in an immunocompetent patient, similar to the cutaneous primary forms.cryptococcosis is a fungal infection caused by cryptococcus neoformans that tends to affect immunocompromised individuals. the fungi are mostly acquired by inhalation, which leads to an initial pulmonary infection. later, other organs - such as the central nervous system and the skin - can be affected by hematogenous spread. in addition, cutaneous contamination can occur by primary inoculation after injuries (primary cutaneous cryptococcosis), whose diagnosis is defined based on the absence of s ...201728300886
scavenger receptor marco orchestrates early defenses and contributes to fungal containment during cryptococcal infection.the scavenger receptor macrophage receptor with collagenous structure (marco) promotes protective innate immunity against bacterial and parasitic infections; however, its role in host immunity against fungal pathogens, including the major human opportunistic fungal pathogen cryptococcus neoformans, remains unknown. using a mouse model of c. neoformans infection, we demonstrated that marco deficiency leads to impaired fungal control during the afferent phase of cryptococcal infection. diminished ...201728298522
the combined rapid detection and species-level identification of yeasts in simulated blood culture using a colorimetric sensor array.a colorimetric sensor array (csa) has been demonstrated to rapidly detect and identify bacteria growing in blood cultures by obtaining a species-specific "fingerprint" of the volatile organic compounds (vocs) produced during growth. this capability has been demonstrated in prokaryotes, but has not been reported for eukaryotic cells growing in culture. the purpose of this study was to explore if a disposable csa could differentially identify 7 species of pathogenic yeasts growing in blood culture ...201728296967
characterization of c-type lectins reveals an unexpectedly limited interaction between cryptococcus neoformans spores and dectin-1.phagocytosis by innate immune cells is an important process for protection against multiple pathologies and is particularly important for resistance to infection. however, phagocytosis has also been implicated in the progression of some diseases, including the dissemination of the human fungal pathogen, cryptococcus neoformans. previously, we identified dectin-1 as a likely phagocytic receptor for c. neoformans spores through the use of soluble components in receptor-ligand blocking experiments. ...201728282442
chemical characterisation and biological activity of leaf essential oils obtained from pistacia terebinthus growing wild in tunisia and sardinia island.in the present work the chemical compositions, measured by gc and gc-ms, of the essential oils obtained by hydrodistillation from leaves of pistacia terebinthus collected in bizerte (tunisia) and baunei (italy) are reported. both essential oils possessed high content of monoterpene hydrocarbons (86.3% and 90.9%, respectively), being α-pinene (62.4 vs. 35.0)%, camphene (3.0 vs. 2.4)%, β-pinene (12.1 vs. 4.5)%, terpinolene (1.7 vs. 35.2)% and β-phellandrene (3.8 vs. 4.5)% the main components. the ...201728278668
a case of disseminated infection with skin manifestation due to non-neoformans and non-gattii cryptococcus in a patient with refractory acute myeloid leukemia.cryptococcus spp. other than cryptococcus neoformans or cryptococcus gattii were previously considered saprophytes and thought to be non-pathogenic to humans. however, opportunistic infections associated with non-neoformans and non-gattii species, such as cryptococcus laurentii and cryptococcus albidus, have increased over the past four decades. we experienced a case of cryptococcosis caused by non-neoformans and non-gattii spp. in a 47-year-old female with refractory acute myeloid leukemia afte ...201728271644
microevolution of serial clinical isolates of cryptococcus neoformans var. grubii and c. gattii.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 1 ...201728270580
connecting virulence pathways to cell-cycle progression in the fungal pathogen cryptococcus neoformans.proliferation and host evasion are critical processes to understand at a basic biological level for improving infectious disease treatment options. the human fungal pathogen cryptococcus neoformans causes fungal meningitis in immunocompromised individuals by proliferating in cerebrospinal fluid. current antifungal drugs target "virulence factors" for disease, such as components of the cell wall and polysaccharide capsule in c. neoformans. however, mechanistic links between virulence pathways and ...201728265742
phosphorus-rich structures and capsular architecture in cryptococcus neoformans.in this study, we aimed to analyze the relationship of phosphorus-rich structures with surface architecture in cryptococcus neoformans.201728262043
the water channel protein aquaporin 1 regulates cellular metabolism and competitive fitness in a global fungal pathogen cryptococcus neoformans.in this study, an aquaporin protein, aqp1, in cryptococcus neoformans, which can lead either saprobic or parasitic lifestyles and causes life-threatening fungal meningitis was identified and characterized. aqp1 expression was rapidly induced (via the hog pathway) by osmotic or oxidative stress. in spite of such transcriptional regulation, aqp1 was found to be largely unnecessary for adaptation to diverse environmental stressors, regardless of the presence of the polysaccharide capsule. the latte ...201728251810
umtco1, a hybrid histidine kinase gene, is essential for the sexual development and virulence of ustilago maydis.hybrid histidine kinase is a part of two-component system that is required for various stress responses and pathogenesis of pathogenic fungi. the tco1 gene in human pathogen cryptococcus neoformans encodes a hybrid histidine kinase and is important for pathogenesis. in the present study, we identified a tco1 gene homolog, umtco1, in the corn smut pathogen ustilago maydis by bioinformatics analysis. to explore the role of umtco1 in the survival of u. maydis under environmental stresses and its pa ...201728237997
transcriptomic and virulence factors analyses of cryptococcus neoformans hypoxia response.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. however, the mechanisms by which the pathogen adapts to the low-oxygen environment in the brain have not been investigated. we isolated a c. neoformans strain with a small capsule from a host tissue, although this strain produces large capsules in normoxic conditions. we hypothesize that this diffe ...201728233445
dynamic protein s-palmitoylation mediates parasite life cycle progression and diverse mechanisms of virulence.eukaryotic parasites possess complex life cycles and utilize an assortment of molecular mechanisms to overcome physical barriers, suppress and/or bypass the host immune response, including invading host cells where they can replicate in a protected intracellular niche. protein s-palmitoylation is a dynamic post-translational modification in which the fatty acid palmitate is covalently linked to cysteine residues on proteins by the enzyme palmitoyl acyltransferase (pat) and can be removed by lyso ...201728228066
comparison of the bruker biotyper and vitek ms matrix-assisted laser desorption/ionization time-of-flight mass spectrometry systems using a formic acid extraction method to identify common and uncommon yeast isolates.matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (maldi-tof ms) allows rapid and accurate identification of clinical yeast isolates. in-tube formic acid/acetonitrile (fa/acn) extraction is recommended prior to the analysis with maldi biotyper, but the direct on-plate fa extraction is simpler. we compared the biotyper with the vitek ms for the identification of various clinically relevant yeast species, focusing on the use of the fa extraction method.201728224768
enzymatic characterization of clinical and environmental cryptococcus neoformans strains isolated in italy.cryptococcus neoformans is an encapsulated yeast causing mainly opportunistic infections. the virulence factors involved in cryptococcosis pathogenesis include the presence and the size of the polysaccharide capsule, the production of melanin by phenoloxidase, the growth at 37°c and the enzyme secretion like proteinase, phospholipase and urease. many other enzymes are secreted by c. neoformans but their role in the fungus virulence is not yet known.201728215482
the southeastern asian house mouse (mus musculus castaneus linn.) as a new passenger host for cryptococcus neoformans var. grubii molecular type vni. 201728204573
correction: mlst-based population genetic analysis in a global context reveals clonality amongst cryptococcus neoformans var. grubii vni isolates from hiv patients in southeastern brazil.[this corrects the article doi: 10.1371/journal.pntd.0005223.].201728199329
[clinical significance of cryptococcus neoformans in faeces of an aids patient]. 201728198172
modulation of replicative lifespan in cryptococcus neoformans: implications for virulence.the fungal pathogen, cryptococcus neoformans, has been shown to undergo replicative aging. old cells are characterized by advanced generational age and phenotypic changes that appear to mediate enhanced resistance to host and antifungal-based killing. as a consequence of this age-associated resilience, old cells accumulate during chronic infection. based on these findings, we hypothesized that shifting the generational age of a pathogenic yeast population would alter its vulnerability to the hos ...201728194146
a population genomics approach to assessing the genetic basis of within-host microevolution underlying recurrent cryptococcal meningitis infection.recurrence of meningitis due to cryptococcus neoformans after treatment causes substantial mortality in hiv/aids patients across sub-saharan africa. in order to determine whether recurrence occurred due to relapse of the original infecting isolate or reinfection with a different isolate weeks or months after initial treatment, we used whole-genome sequencing (wgs) to assess the genetic basis of infection in 17 hiv-infected individuals with recurrent cryptococcal meningitis (cm). comparisons reve ...201728188180
cerebral cryptococcoma mimicking glioblastoma.cryptococcus neoformans and c. gattii cause invasive fungal disease, with meningitis being the most common manifestation of central nervous system (cns) disease. encapsulated cryptococcomas occur rarely, predominantly in immunocompetent hosts, usually related to c. gattii our patient was an immunocompetent man who presented with headache and a large cystic cns lesion thought to be glioblastoma. biopsy of a concomitant lung lesion confirmed cryptococcoma and empiric antifungal therapy was started ...201728188169
troponoids can inhibit growth of the human fungal pathogen cryptococcus neoformans.cryptococcus neoformans is a pathogen that is common in immunosuppressed patients. it can be treated with amphotericin b and fluconazole, but the mortality rate remains 15 to 30%. thus, novel and more effective anticryptococcal therapies are needed. the troponoids are based on natural products isolated from western red cedar, and have a broad range of antimicrobial activities. extracts of western red cedar inhibit the growth of several fungal species, but neither western red cedar extracts nor t ...201728167553
disseminated cryptococcosis with rapidly growing lung nodules in an end-stage renal disease patient.a 73-year-old man with type 2 diabetes mellitus and end-stage renal disease was diagnosed with acute myocardial infarction. he required continuous dialysis after percutaneous coronary intervention. subsequently, multiple nodules were discovered in both lungs for the first time, and cryptococcus neoformans was isolated from the patient's sputum, blood, bilateral pleural fluid, and cerebrospinal fluid cultures, resulting in a diagnosis of disseminated cryptococcosis. this case represents an invalu ...201728154287
repurposing approach identifies auranofin with broad spectrum antifungal activity that targets mia40-erv1 pathway.current antifungal therapies have limited effectiveness in treating invasive fungal infections. furthermore, the development of new antifungal is currently unable to keep pace with the urgent demand for safe and effective new drugs. auranofin, an fda-approved drug for the treatment of rheumatoid arthritis, inhibits growth of a diverse array of clinical isolates of fungi and represents a new antifungal agent with a previously unexploited mechanism of action. in addition to auranofin's potent anti ...201728149831
pho4 is essential for dissemination of cryptococcus neoformans to the host brain by promoting phosphate uptake and growth at alkaline ph.phosphate acquisition by fungi is regulated by the phosphate-sensing and acquisition (pho) signaling pathway. cryptococcus neoformans disseminates from the lung to the brain and is the commonest cause of fungal meningitis worldwide. to investigate the contribution of pho signaling to cryptococcal dissemination, we characterized a transcription factor knockout strain (hlh3δ/pho4δ) defective in phosphate acquisition. despite little similarity with other fungal pho4 proteins, hlh3/pho4 functioned l ...201728144629
rim pathway-mediated alterations in the fungal cell wall influence immune recognition and inflammation.compared to other fungal pathogens, cryptococcus neoformans is particularly adept at avoiding detection by innate immune cells. to explore fungal cellular features involved in immune avoidance, we characterized cell surface changes of the c. neoformans rim101δ mutant, a strain that fails to organize and shield immunogenic epitopes from host detection. these cell surface changes are associated with an exaggerated, detrimental inflammatory response in mouse models of infection. we determined that ...201728143983
trojan horse transit contributes to blood-brain barrier crossing of a eukaryotic pathogen.the blood-brain barrier (bbb) protects the central nervous system (cns) by restricting the passage of molecules and microorganisms. despite this barrier, however, the fungal pathogen cryptococcus neoformans invades the brain, causing a meningoencephalitis that is estimated to kill over 600,000 people annually. cryptococcal infection begins in the lung, and experimental evidence suggests that host phagocytes play a role in subsequent dissemination, although this role remains ill defined. addition ...201728143979
complex roles of annexin a2 in host blood-brain barrier invasion by cryptococcus neoformans.fungal transversal across the brain microvascular endothelial cells (bmecs) is the essential step for the development of cryptococcal meningoencephalitis. annexin a2 (anxa2) is an important signaling protein involved in several intracellular processes such as membrane trafficking, endocytosis, and exocytosis.201728130864
melanin is effective in protecting fast and slow growing fungi from various types of ionizing radiation.melanin is a ubiquitous pigment with unique physicochemical properties. the resistance of melanized fungi to cosmic and terrestrial ionizing radiation suggests that melanin also plays a pivotal role in radioprotection. in this study, we compared the effects of densely-ionizing deuterons and sparsely-ionizing x-rays on two microscopic fungi capable of melanogenesis. we utilized the fast-growing pathogenic basiodiomycete forming an induced dopa-melanin, cryptococcus neoformans (cn); and the slow-g ...201728127878
report on novel environmental niches for cryptococcus neoformans and cryptococcus gattii in colombia: tabebuia guayacan and roystonea regia.knowledge of the environmental distribution of c. neoformans/c. gattii is important in the epidemiology and ecology of the etiological agent, which causes cryptococcosis, a deadly disease worldwide. the aim of this report is to describe the presence of c. neoformans/c. gattii in new environmental niches in colombia. a total of 837 environmental samples were collected from six different species of trees across four cities; molecular type was determined by pcr fingerprinting and rflp. molecular ty ...201728115408
nabscessins a and b, aminocyclitol derivatives from nocardia abscessus ifm 10029(t).two new aminocyclitol amide derivatives, nabscessins a (1) and b (2), were isolated from the culture broth of a pathogenic actinomycete species, nocardia abscessus ifm 10029(t). the structures of nabscessins a and b were elucidated by spectral studies, and the compounds showed antifungal activity against cryptococcus neoformans, with ic50 values of 32 and 16 μg/ml, respectively.201728112922
dectin-3 is not required for protection against cryptococcus neoformans infection.c-type lectin receptors (clrs) are diverse, trans-membrane proteins that function as pattern recognition receptors (prrs) which are necessary for orchestrating immune responses against pathogens. clrs have been shown to play a major role in recognition and protection against fungal pathogens. dectin-3 (also known as mcl, clecsf8, or clec4d) is a myeloid cell-specific clr that recognizes mycobacterial trehalose 6,6'-dimycolate (tdm) as well as α-mannans present in the cell wall of fungal pathogen ...201728107361
the case for adopting the "species complex" nomenclature for the etiologic agents of cryptococcosis.cryptococcosis is a potentially lethal disease of humans/animals caused by cryptococcus neoformans and cryptococcus gattii. distinction between the two species is based on phenotypic and genotypic characteristics. recently, it was proposed that c. neoformans be divided into two species and c. gattii into five species based on a phylogenetic analysis of 115 isolates. while this proposal adds to the knowledge about the genetic diversity and population structure of cryptococcosis agents, the publis ...201728101535
mlst-based population genetic analysis in a global context reveals clonality amongst cryptococcus neoformans var. grubii vni isolates from hiv patients in southeastern brazil.cryptococcosis is an important fungal infection in immunocompromised individuals, especially those infected with hiv. in brazil, despite the free availability of antiretroviral therapy (art) in the public health system, the mortality rate due to cryptococcus neoformans meningitis is still high. to obtain a more detailed picture of the population genetic structure of this species in southeast brazil, we studied 108 clinical isolates from 101 patients and 35 environmental isolates. among the patie ...201728099434
the role of macrophages in the susceptibility of fc gamma receptor iib deficient mice to cryptococcus neoformans.dysfunctional polymorphisms of fcγriib, an inhibitory receptor, are associated with systemic lupus erythaematosus (sle). cryptococcosis is an invasive fungal infection in sle, perhaps due to the de novo immune defect. we investigated cryptococcosis in the fcγriib-/- mouse-lupus-model. mortality, after intravenous c. neoformans-induced cryptococcosis, in young (8-week-old) and older (24-week-old) fcγriib-/- mice, was higher than in age-matched wild-types. severe cryptococcosis in the fcγriib-/- m ...201728074867
different lymphocyte populations direct dichotomous eosinophil or neutrophil responses to pulmonary cryptococcus infection.many pulmonary infections elicit lymphocyte responses that lead to an accumulation of granulocytes in the lungs. a variety of lymphocytes are capable of directing eosinophils or neutrophils to the lungs, but the contribution of each subset remains enigmatic. in this study, we used a murine model to examine lymphocyte subsets that ultimately drive the eosinophil or neutrophil response to infection with the fungal pathogen cryptococcus neoformans. we show that granulocytes are produced in the bone ...201728069805
gmp synthase is required for virulence factor production and infection by cryptococcus neoformans.over the last four decades the hiv pandemic and advances in medical treatments that also cause immunosuppression have produced an ever-growing cohort of individuals susceptible to opportunistic pathogens. of these, aids patients are particularly vulnerable to infection by the encapsulated yeast cryptococcus neoformans most commonly found in the environment in purine-rich bird guano, c. neoformans experiences a drastic change in nutrient availability during host infection, ultimately disseminatin ...201728062578
a p4-atpase subunit of the cdc50 family plays a role in iron acquisition and virulence in cryptococcus neoformans.the pathogenic fungus cryptococcus neoformans delivers virulence factors such as capsule polysaccharide to the cell surface to cause disease in vertebrate hosts. in this study, we screened for mutants sensitive to the secretion inhibitor brefeldin a to identify secretory pathway components that contribute to virulence. we identified an ortholog of the cell division control protein 50 (cdc50) family of the noncatalytic subunit of type iv p-type atpases (flippases) that establish phospholipid asym ...201728061020
corticosteroid-induced cryptococcal meningitis in patient without hiv.cryptococcus neoformans is the most frequent cause of fungal meningitis in humans. cryptococcus affects people of all ages and has a worldwide distribution. it is the fourth most common infection in aids (cd4 counts <100/mm(3)). cases also occur in patients with other forms of immunosuppression and in apparently immunocompetent individuals. chronic high-dose steroid may precipitate such an immunocompromised state and thus create susceptibility to fungal infections. in our case, we describe a 14- ...201728052943
cryptococcal infection of the ventriculoperitoneal shunt in an hiv-infected patient with an excellent immunovirologic status.cryptococcus spp. is a rare cause of ventriculoperitoneal shunt (vps) infection, with a variable clinical presentation. diagnosis and treatment of this entity are challenging.201728049033
a family of secretory proteins is associated with different morphotypes in cryptococcus neoformans.cryptococcus neoformans, an opportunistic human fungal pathogen, can undergo a yeast-to-hypha transition in response to environmental cues. this morphological transition is associated with changes in the expression of cell surface proteins. the cryptococcus cell surface and secreted protein cfl1 was the first identified adhesin in the basidiomycota. cfl1 has been shown to regulate morphology, biofilm formation, and intercellular communication. four additional homologs of cfl1 are harbored by the ...201728039134
physiological differences in cryptococcus neoformans strains in vitro versus in vivo and their effects on antifungal susceptibility.cryptococcus neoformans is an environmentally ubiquitous fungal pathogen that primarily causes disease in people with compromised immune systems, particularly those with advanced aids. there are estimated to be almost 1 million cases per year of cryptococcal meningitis in patients infected with human immunodeficiency virus, leading to over 600,000 annual deaths, with a particular burden in sub-saharan africa. amphotericin b (amb) and fluconazole (flc) are key components of cryptococcal meningiti ...201728031206
synthesis and antifungal in vitro evaluation of pyrazolo[3,4-b]pyridines derivatives obtained by aza-diels-alder reaction and microwave irradiation.a series of pyrazolo[3,4-b]pyridines were prepared by a microwave-assisted aza-diels-alder reaction between pyrazolylformimidamides 1 and β-nitrostyrenes 2 in toluene as the solvent. this procedure provides a simple one-step and environmentally friendly methodology with good yields for the synthesis of these compounds. all compounds were tested for antifungal activity against two clinically important fungi candida albicans and cryptococcus neoformans. within the compounds of the series bearing a ...201727890876
ebselen exerts antifungal activity by regulating glutathione (gsh) and reactive oxygen species (ros) production in fungal cells.ebselen, an organoselenium compound and a clinically safe molecule has been reported to possess potent antifungal activity, but its antifungal mechanism of action and in vivo antifungal activity remain unclear.201727712973
antimicrobial and cytotoxicity properties of the organic solvent fractions of clerodendrum myricoides (hochst.) r. br. ex vatke: kenyan traditional medicinal plant.clerodendrum myricoides is a kenyan herbal plant used in the management of respiratory diseases. in the current study, we investigated in vitro antimicrobial activity, cytotoxicity, and phytochemical screening of c. myricoides.201727366347
evaluation of the antimicrobial activity of the mastoparan polybia-mpii isolated from venom of the social wasp pseudopolybia vespiceps testacea (vespidae, hymenoptera).mastoparans, a class of peptides found in wasp venom, have significant effects following a sting as well as useful applications in clinical practice. among these is their potential use in the control of micro-organisms that cause infectious diseases with a significant impact on society. thus, the present study describes the isolation and identification of a mastoparan peptide from the venom of the social wasp pseudopolybia vespiceps and evaluated its antimicrobial profile against bacteria (staph ...201728108242
synthesis and biological evaluation of novel 2-aminonicotinamide derivatives as antifungal agents.based on the structures of the reported compounds g884 [n-(3-(pentan-2-yloxy)phenyl)nicotinamide], e1210 [3-(3-(4-((pyridin-2-yloxy)methyl)benzyl)isoxazol-5-yl)pyridin-2-amine], and 10 b [2-amino-n-((5-(3-fluorophenoxy)thiophen-2-yl)methyl)nicotinamide], which inhibit the biosynthesis of glycosylphosphatidylinositol (gpi)-anchored proteins in fungi, a series of novel 2-aminonicotinamide derivatives were designed, synthesized, and evaluated for in vitro antifungal activity. most of these compound ...201728071858
utilization of size polymorphism in its1 and its2 regions for identification of pathogenic yeast species.despite the existence of a variety of available yeast identification strategies, easier and more cost-effective methods are required for routine use in clinical laboratories. the internal transcribed spacer (its) regions of fungal rrna genes exhibit variable sizes depending on the yeast species. in the present study, fragment size polymorphism (fsp) analysis of the its1 and its2 regions for identification of the clinically most important yeast species was assessed. the its1 and its2 regions of 1 ...201728068213
discovery of biphenyl imidazole derivatives as potent antifungal agents: design, synthesis, and structure-activity relationship studies.fungal infections have became a serious medical problem due to their high incidence and mortality. we describe the discovery and structure-activity relationships studies (sars) of a series of novel biphenyl imidazole derivatives with excellent antifungal activities against candida albicans and cryptococcus neoformans. the most promising compounds 12f-g and 19a-b exhibited excellent activity with minimum inhibitory concentration (mic) values in the range of 0.03125-2μg/ml. preliminary mechanism s ...201727955926
synthesis of novel quinoline-based 4,5-dihydro-1h-pyrazoles as potential anticancer, antifungal, antibacterial and antiprotozoal agents.a new series of n-substituted 2-pyrazolines 9a-f, 10a-f, 11a-f, 12a-f and 13a-f were obtained from the cyclocondensation reaction of [(7-chloroquinolin-4-yl)amino]chalcones 8a-f with hydrazine hydrate and its derivatives. fourteen of the synthesized compounds including the starting chalcones were selected by us national cancer institute (nci) for testing their anticancer activity against 60 different human cancer cell lines, with the most important gi50 values ranging from 0.28 to 11.7 μm (0.13- ...201728329730
assessment of safe bioactive doses of foeniculum vulgare mill. essential oil from portugal.this study was designed to evaluate the antifungal activity of foeniculum vulgare essential oil; concomitantly, the safety of bioactive doses was also unveiled, for the first time, in several mammalian cells. the chemical characterisation was made by gc and gc-ms. antifungal activity was evaluated against yeasts, dermatophytes and aspergillus strains and germ tube inhibition assay was evaluated using candida albicans. cell viability was assessed by the mtt assay. the main constituents of the oil ...201728278624
utilization of size polymorphism in its1 and its2 regions for identification of pathogenic yeast species.despite the existence of a variety of available yeast-identification strategies, easier and more cost-effective methods are required for routine use in clinical laboratories. the internal transcribed spacer (its) regions of fungal rrna genes exhibit variable sizes depending on the yeast species. in the present study, fragment size polymorphism (fsp) analysis of the its1 and its2 regions for identification of the clinically most important yeast species was assessed.201728260588
blocking two-component signalling enhances candida albicans virulence and reveals adaptive mechanisms that counteract sustained sapk activation.the ypd1 phosphorelay protein is a central constituent of fungal two-component signal transduction pathways. inhibition of ypd1 in saccharomyces cerevisiae and cryptococcus neoformans is lethal due to the sustained activation of the 'p38-related' hog1 stress-activated protein kinase (sapk). as two-component signalling proteins are not found in animals, ypd1 is considered to be a prime antifungal target. however, a major fungal pathogen of humans, candida albicans, can survive the concomitant sus ...201728135328
microbiology of cooked and dried edible mediterranean field crickets (gryllus bimaculatus) and superworms (zophobas atratus) submitted to four different heating treatments.to increase the shelf life of edible insects, modern techniques (e.g. freeze-drying) add to the traditional methods (degutting, boiling, sun-drying or roasting). however, microorganisms become inactivated rather than being killed, and when rehydrated, many return to vegetative stadia. crickets (gryllus bimaculatus) and superworms (zophobas atratus) were submitted to four different drying techniques (t1 = 10' cooking, 24 h drying at 60℃; t2 = 10' cooking, 24 h drying at 80℃; t3 = 30' cooking, 12  ...201727235993
antimicrobial assay and genetic screening of selected freshwater cyanobacteria and identification of a biomolecule dihydro-2h-pyran-2-one derivative.explorations of freshwater cyanobacteria as antimicrobial (bacteria, fungi and methicillin-resistant staphylococcus aureus (mrsa) strains) drug resource using bioassay, nrps (non-ribosomal polypeptide synthetase) and pks (polyketide synthase) genes, as well as in silico approach.201728004519
approach to fungal infections in human immunodeficiency virus-infected individuals: pneumocystis and beyond.many fungi cause pulmonary disease in patients with human immunodeficiency virus (hiv) infection. pathogens include pneumocystis jirovecii, cryptococcus neoformans, aspergillus spp, histoplasma capsulatum, coccidioides spp, blastomyces dermatitidis, paracoccidioides brasiliensis, talaromyces marneffei, and emmonsia spp. because symptoms are frequently nonspecific, a high index of suspicion for fungal infection is required for diagnosis. clinical manifestations of fungal infection in hiv-infected ...201728797489
imaging spectrum of invasive fungal and fungal-like infections.invasive fungal and fungal-like infections contribute to substantial morbidity and mortality in immunocompromised individuals. the incidence of these infections is increasing-largely because of rising numbers of immunocompromised patients, including those with neutropenia, human immunodeficiency virus, chronic immunosuppression, indwelling prostheses, burns, and diabetes mellitus, and those taking broad-spectrum antibiotics. invasive fungal pathogens include primary mycotic organisms such as his ...201728622118
evaluation of primitive ground water supplies as a risk factor for the development of major waterborne zoonosis in egyptian children living in rural areas.endemic waterborne zoonosis frequently occurs in both developed and less developed countries. thus, bio-surveillance of waterborne zoonosis is a "necessity" for the implementation of effective preventive public health measures in egyptian rural areas. the primitive individual water supplies created by the rural agriculture population, primarily from ground water, usually maximize the customers' exposure to impurity pathogens via diffused humans and animal excreta or wastages. the current study a ...201728843417
phosphate acquisition and virulence in human fungal pathogens.the ability of pathogenic fungi to acquire essential macro and micronutrients during infection is a well-established virulence trait. recent studies in the major human fungal pathogens candida albicans and cryptococcus neoformans have revealed that acquisition of the essential macronutrient, phosphate, is essential for virulence. the phosphate sensing and acquisition pathway in fungi, known as the pho pathway, has been extensively characterized in the model yeast saccharomyces cerevisiae. in thi ...201728829379
two plant-derived aporphinoid alkaloids exert their antifungal activity by disrupting mitochondrial iron-sulfur cluster biosynthesis.eupolauridine and liriodenine are plant-derived aporphinoid alkaloids that exhibit potent inhibitory activity against the opportunistic fungal pathogens candida albicans and cryptococcus neoformans however, the molecular mechanism of this antifungal activity is unknown. in this study, we show that eupolauridine 9591 (e9591), a synthetic analog of eupolauridine, and liriodenine methiodide (lmt), a methiodide salt of liriodenine, mediate their antifungal activities by disrupting mitochondrial iron ...201728821607
assessment of in vitro antifungal efficacy and in vivo toxicity of amphotericin b-loaded plga and plga-peg blend nanoparticles.amphotericin b (amb) is widely applied in treatment of systemic fungal infections. however, the emergence of severe adverse effects, such as nephrotoxicity, hepatotoxicity and hemolytic anemia, can limit its clinical use. poly(lactide-co-glycolide) (plga) or poly(lactide-co-glycolide)-poly(ethylene glycol) (plga-peg) blend nanoparticles containing amb were developed with the aim to decrease amb toxicity and propose the oral route for amb delivery. nanoparticles were characterized by particle siz ...201728797532
heat shock protein 90 localizes to the surface and augments virulence factors of cryptococcus neoformans.thermotolerance is an essential attribute for pathogenesis of cryptococcus as exemplified by the fact that only two species in the genus, which can grow at 37°c, are human pathogens. species which have other virulence factors including capsule formation and melanisation, but lack the ability to propagate at 37°c are not pathogenic. in another related fungal pathogen, candida albicans, heat shock protein 90 has been implicated to be a central player in commanding pathogenicity by governing yeast ...201728783748
detection of fungi from an indoor environment using loop-mediated isothermal amplification (lamp) method.loop-mediated isothermal amplification (lamp) is a useful dna detection method with high specificity and sensitivity. the lamp reaction is carried out within a short time at a constant temperature without the need for thermal cycling. we developed a lamp primer set for detecting a wide range of fungi by aligning the sequences of the large subunit ribosomal rna gene of candida albicans (ascomycota), cryptococcus neoformans (basidiomycota), and mucor racemosus (mucorales). the threshold of c. albi ...201728659561
anti-cryptococcus phenalenones and cyclic tetrapeptides from auxarthron pseudauxarthron.auxarthrones a-e (1-5), five new phenalenones, and two new naturally occurring cyclic tetrapeptides, auxarthrides a (7) and b (8), were obtained from three different solvent extracts of cultures of the coprophilous fungus auxarthron pseudauxarthron. auxarthrones c (3) and e (5) possess an unusual 7a,8-dihydrocyclopenta[a]phenalene-7,9-dione ring system that has not been previously observed in natural products. formation of 1-5 was found to be dependent on the solvent used for culture extraction. ...201728657331
fluconazole-induced ploidy change in cryptococcus neoformans results from the uncoupling of cell growth and nuclear division.cryptococcus neoformans is a pathogenic yeast that causes lethal cryptococcal meningitis in immunocompromised patients. one of the challenges in treating cryptococcosis is the development of resistance to azole antifungals. previous studies linked azole resistance to elevated numbers of copies of critical resistance genes in aneuploid cells. however, how aneuploidy is formed in the presence of azole drugs remains unclear. this study showed that treatment with inhibitory concentrations of an azol ...201728630940
design, synthesis and evaluation of aromatic heterocyclic derivatives as potent antifungal agents.to further enhance the anti-aspergillus efficacy of our previously discovered antifungal lead compounds (1), a series of aromatic heterocyclic derivatives were designed, synthesized and evaluated for in vitro antifungal activity. many of the target compounds showed good inhibitory activity against candida albicans and cryptococcus neoformans. in particular, the isoxazole nuclei were more suited for improving the activity against aspergillus spp. among these compounds, 2-f substituted analogues 2 ...201728558334
antifungal toxicity of linear geranylphenol. influence of oxigenate substituents.twenty four linear geranylphenols were evaluated for their antifungal properties against atcc and clinical isolates of candida albicans and cryptococcus neoformans. for the analysis of their antifungal behavior the compounds were grouped into two series: (i) compounds with only one geranyl substituent on the benzene ring and (ii) compounds with two geranyl moieties on the benzene ring. results showed that compounds of series (i) present better antifungal activities than those of series (ii). in ...201728528250
the yeasts phosphorelay systems: a comparative view.cells contain signal transduction pathways that mediate communication between the extracellular environment and the cell interior. these pathways control transcriptional programs and posttranscriptional processes that modify cell metabolism in order to maintain homeostasis. one type of these signal transduction systems are the so-called two component systems (tcs), which conduct the transfer of phosphate groups between specific and conserved histidine and aspartate residues present in at least t ...201728470426
the antibiotic polymyxin b exhibits novel antifungal activity against fusarium species.the genus fusarium comprises many species, including fusarium oxysporum, fusarium solani, fusarium graminearum and fusarium verticillioides, and causes severe infections in plants and humans. in clinical settings, fusarium is the third most frequent mould to cause invasive fungal infections after aspergillus and the mucorales. f. solani and f. oxysporum are the most prevalent fusarium spp. causing clinical disease. however, few effective antifungal drugs are available to treat human and plant fu ...201728433743
mismatch repair of dna replication errors contributes to microevolution in the pathogenic fungus cryptococcus neoformans.the ability to adapt to a changing environment provides a selective advantage to microorganisms. in the case of many pathogens, a large change in their environment occurs when they move from a natural setting to a setting within a human host and then during the course of disease development to various locations within that host. two clinical isolates of the human fungal pathogen cryptococcus neoformans were identified from a collection of environmental and clinical strains that exhibited a mutat ...201728559486
current status of taxonomy of pathogenic yeasts.fungal taxonomy has been reconstructed on the basis of genome information, and new nomenclatural rules have been enacted from 2013. it has been proposed that cryptococcus neoformans and cryptococcus gattii be reclassified into two species (c. neoformans and cryptococcus deneoformans) and five species (c. gattii, cryptococcus bacillisporus, cryptococcus deuterogattii, cryptococcus tetragattii, and cryptococcus decagattii), respectively. the genus trichosporon has been reclassified into five gener ...201728855483
cryptococcal lung infections.cryptococcus is among the most common invasive fungal pathogens globally and is one of the leading causes of acquired immunodeficiency virus-related deaths. cryptococcus neoformans and cryptococcus gattii are the most clinically relevant species and account for most cryptococcal disease. pulmonary manifestations can range from mild symptoms to life-threatening infection. treatment is tailored based on the severity of pulmonary infection, the presence of disseminated or central nervous system dis ...201728797488
cryptococcosis in patients with diabetes mellitus ii in mainland china: 1993-2015.diabetes mellitus ii (dm ii) is a newly defined independent factor contributing to the morbidity and mortality of cryptococcosis. this retrospective case analysis aims to explore the epidemiology, clinical profile and strain characteristics of cryptococcosis in chinese dm ii patients. this study included 30 cases of cryptococcosis with dm ii occurring from 1993 to 2015 in mainland china. the hospital-based prevalence of cryptococcosis in dm ii was 0.21%. the mean age of the patients was 56.1 yea ...201728857298
recognition of cryptococcus neoformans by pattern recognition receptors and its role in host defense to this infection.cryptococcus neoformans is a yeast-type opportunistic fungal pathogen with a capsule structure consisting of polysaccharides, such as glucuronoxylomannan and galactoxylomannan, and infects the lungs via an air-borne route. most healthy individuals undergo asymptomatic infection with granulomatous lesions in the lungs caused by c. neoformans. however, immunocompromised hosts with severely impaired cellular immunity, such as those with acquired immune deficiency syndrome (aids), often suffer from ...201728855484
naïve b cells reduce fungal dissemination in cryptococcus neoformans infected rag1(-/-) mice.igm and b-1 cell deficient mice exhibit early c. neoformans dissemination from lungs to brain, but a definitive role for b cells in conferring resistance to c. neoformans dissemination has not been established. to address this question, we developed an intranasal (i.n.) c. neoformans infection model in b and t cell deficient rag1(-/-) mice and found they also exhibit earlier fungal dissemination and higher brain cfu than wild-type c57bl/6 (wild-type) mice. to probe the effect of b cells on funga ...201728837391
correction: macrophage mitochondrial and stress response to ingestion of cryptococcus neoformans. 201728827389
capsule enlargement in cryptococcus neoformans is dependent on mitochondrial activity.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 ...201728824559
mannose surfaces exhibit self-latching, water structuring, and resilience to chaotropes: implications for pathogen virulence.several viral and fungal pathogens, including hiv, sars, dengue, ebola, and cryptococcus neoformans, display a preponderance of mannose residues on their surface, particularly during the infection cycle or in harsh environments. the innate immune system, on the other hand, abounds in mannose receptors which recognize mannose residues on pathogens and trigger their phagocytosis. we pose the question if there is an advantage for pathogens to display mannose on their surface, despite these residues ...201728817934
clinical evaluation of the antifungal effect of sertraline in the treatment of cryptococcal meningitis in hiv patients: a single mexican center experience.cryptococcal meningitis is a potentially fatal fungal infection associated with a significant attributable morbidity and mortality, especially among hiv/aids patients. the first-line therapy for the treatment of this clinical entity is the combinatory therapy of amphotericin b plus flucytosine. however, the high cost, toxic effects, and limited repertoire of effective antifungal drugs have led to the investigation of novel molecules. this is a prospective, double-blinded, and randomized study pe ...201728815430
depsidones and an α-pyrone derivative from simpilcillium sp. psu-h41, an endophytic fungus from hevea brasiliensis leaf.nine previously undescribed depsidones (simplicildones a-i) and one previously undescribed α-pyrone (simplicilopyrone) were isolated from the endophytic fungus simplicillium sp. psu-h41 along with 11 known compounds. their structures were established by extensive spectroscopic analysis. simplicildone a and known botryorhodine c displayed weak antibacterial against staphylococcus aureus with equal mic values of 32 μg/ml. additionally, botryorhodine c was active against methicillin-resistant s. au ...201728803995
subarachnoid small vein occlusion due to inflammatory fibrosis-a possible mechanism for cerebellar infarction in cryptococcal meningoencephalitis: a case report.cryptococcal meningoencephalitis (cm) causes cerebral infarction, typically, lacunar infarction in the basal ganglia. however, massive cerebral infarction leading to death is rare and its pathophysiology is unclear. we report a case of cm causing massive cerebellar infarction, which led to cerebral herniation and death.201728793877
cryptococcus neoformans and c. gattii isolates from both hiv-infected and uninfected patients: antifungal susceptibility and outcome of cryptococcal disease.one of the factors causing treatment failure in cryptococcosis is the resistance of cryptococcus spp. to antifungal drugs, which has motivated the susceptibility assessment of isolates from patients with cryptococcosis, different clinical conditions and infections outcomes. clinical isolates of cryptococcus spp. from three different groups of patients were studied in the present investigation: 19 hiv-positive patients with relapsing and/or refractory meningitis (group 1), 30 hiv-positive patient ...201728793019
disseminated cryptococcal infection in a patient who had kidney transplant: discrepancy between clinical symptoms and microbiological findings.a 29-year-old man complained of a 2-day history of frontal headache and new-onset fever but no other symptoms. two months prior to admission, he underwent his third kidney transplantation. clinical and laboratory examinations were unremarkable. brain mri showed a meningeal irritation consistent with viral meningitis. a diagnosis of cryptococcal meningitis and fungaemia was made after detection of a remarkably high and visible load of cryptococcus neoformans in the cerebrospinal fluid.201728775082
fungal infections in hiv/aids.fungi are major contributors to the opportunistic infections that affect patients with hiv/aids. systemic infections are mainly with pneumocystis jirovecii (pneumocystosis), cryptococcus neoformans (cryptococcosis), histoplasma capsulatum (histoplasmosis), and talaromyces (penicillium) marneffei (talaromycosis). the incidence of systemic fungal infections has decreased in people with hiv in high-income countries because of the widespread availability of antiretroviral drugs and early testing for ...201728774701
thiocarbonyl ylide chemistry enables a concise synthesis of (±)-hippolachnin a.hippolachnin a (1) is an antifungal polyketide that bristles with ethyl groups mounted onto a caged heterotricyclic core. it has shown potent activity against cryptococcus neoformans, a yeast that can affect immunocompromised patients as an opportunistic pathogen. herein we describe a concise, diversifiable, and scalable synthesis of (±)-hippolachnin a (1). it features a powerful photochemical opening step, a diastereoselective addition of an ethyl cuprate and an unusual strategy to install two ...201728753024
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