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meningitis admitted to a military hospital: a retrospective case series.meningitis is a common admission diagnosis. no case series or descriptive studies on meningitis have recently been published. additionally, no recent data exist on meningitis in the u.s. military health system. we reviewed charts of adult patients admitted to naval medical center san diego between january 2004 and december 2008 with an admission diagnosis of meningitis. charts were excluded if they did not meet our case definition of meningitis, if missing data, or if meningitis was nosocomial o ...201223113452
systemic fungal infections in patients with human inmunodeficiency virus.histoplasmosis is a systemic infection caused by the dimorphic fungus histoplasma capsulatum. in immunocompromised patients, primary pulmonary infection can spread to the skin and meninges. clinical manifestations appear in patients with a cd4(+) lymphocyte count of less than 150 cells/μl. coccidioidomycosis is a systemic mycosis caused by coccidioides immitis and coccidioides posadasii. it can present as diffuse pulmonary disease or as a disseminated form primarily affecting the central nervous ...201423107866
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
[characteristics of the eukaryotic community structure in acid mine drainage lake in anhui province, china].we characterized eukaryotic community structure and the relationship between the community structure and environmental factors in acidic mine drainage (amd) lake of a sulfide mine in anhui province, china.201223115972
cloning of the lentinula edodes b mating-type locus and identification of the genetic structure controlling b mating.during the life cycle of heterothallic tetrapolar agaricomycetes such as lentinula edodes (berk.) pegler, the mating type system, composed of unlinked a and b loci, plays a vital role in controlling sexual development and resulting formation of the fruit body. l. edodes is produced worldwide for consumption and medicinal purposes, and understanding its sexual development is therefore of great importance. a considerable amount of mating type factors has been indicated over the past decades but fe ...201324029079
cryptococcal meningitis in a goat--a case report.cryptococcus spp. are saprophytic and opportunistic fungal pathogens that are known to cause severe disease in immunocompromised animals. in goats there are reports of clinical cryptococcal pneumonia and mastitis but not of meningitis.201424708822
chest radiography for predicting the cause of febrile illness among inpatients in moshi, tanzania.to describe chest radiographic abnormalities and assess their usefulness for predicting causes of fever in a resource-limited setting.201323809268
environmental isolation, biochemical identification, and antifungal drug susceptibility of cryptococcus species.the incidence of opportunistic fungal infections has increased in recent years and is considered an important public health problem. among systemic and opportunistic mycoses, cryptococcosis is distinguished by its clinical importance due to the increased risk of infection in individuals infected by human immunodeficiency virus.201424474019
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
cryptococcus flips its lid - membrane phospholipid asymmetry modulates antifungal drug resistance and virulence.human fungal infections are increasing in prevalence and acquisition of antifungal drug resistance, while our antifungal drug armamentarium remains very limited, constituting a significant public health problem. despite the fact that prominent antifungal drugs target the fungal cell membrane, very little is known about how fungal membrane biology regulates drug-target interactions. asymmetrical phospholipid distribution is an essential property of biological membranes, which is maintained by a g ...201628357373
first case of mixed infection with cryptococcus deuterogattii and cryptococcus neoformans vni in an ivorian hiv-positive patient.cryptococcal meningitis (cm) may be caused by several species of cryptococcus.201628348767
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
putative orotate transporter of cryptococcus neoformans, oat1, is a member of the ncs1/prt transporter super family and its loss causes attenuation of virulence.it is well known that 5-fluoroorotic acid (5-foa)-resistant mutants isolated from wild-type cryptococcus neoformans are exclusively either ura3 or ura5 mutants. unexpectedly, many of the 5-foa-resistant mutants isolated in our selective regime were ura(+). we identified cnm00460 as the gene responsible for these mutations. cnm00460 belongs to the nucleobase cation symporter 1/purine-related transporter (ncs1/prt) super family of fungal transporters, representative members of which are uracil tra ...201628011993
discovery and characterization of a peptoid with antifungal activity against cryptococcus neoformans.studies show there is an increasing rate of fungal infections, especially in immunocompromised patients and treatments for fungal genera, such as aspergillus, candida, and cryptococcus, carry significant cytotoxicity with an increasing prevalence of antifungal resistance. we have previously reported a high-throughput assay for identifying peptoids with antimicrobial properties from combinatorial libraries. here we report the application of this assay in identifying a peptoid with antifungal prop ...201627994753
distribution of the o-acetyl groups and β-galactofuranose units in galactoxylomannans of the opportunistic fungus cryptococcus neoformans.galactoxylomannans (galxms) are a mixture of neutral and acidic capsular polysaccharides produced by the opportunistic fungus cryptococcus neoformans that exhibit potent suppressive effects on the host immune system. previous studies describing the chemical structure of c. neoformans galxms have reported species without o-acetyl substituents. herein we describe that c. neoformans grown in capsule-inducing medium produces highly o-acetylated galxms. the location of the o-acetyl groups was determi ...201627986834
primary cutaneous cryptococcal infection with subsequent erythema nodosum in a 10-year-old immunocompetent girl. 201627981228
integrated activity and genetic profiling of secreted peptidases in cryptococcus neoformans reveals an aspartyl peptidase required for low ph survival and virulence.the opportunistic fungal pathogen cryptococcus neoformans is a major cause of mortality in immunocompromised individuals, resulting in more than 600,000 deaths per year. many human fungal pathogens secrete peptidases that influence virulence, but in most cases the substrate specificity and regulation of these enzymes remains poorly understood. the paucity of such information is a roadblock to our understanding of the biological functions of peptidases and whether or not these enzymes are viable ...201627977806
investigating conservation of the cell-cycle-regulated transcriptional program in the fungal pathogen, cryptococcus neoformans.the pathogenic yeast cryptococcus neoformans causes fungal meningitis in immune-compromised patients. cell proliferation in the budding yeast form is required for c. neoformans to infect human hosts, and virulence factors such as capsule formation and melanin production are affected by cell-cycle perturbation. thus, understanding cell-cycle regulation is critical for a full understanding of virulence factors for disease. our group and others have demonstrated that a large fraction of genes in sa ...201627918582
csn1201, a subunit of the cop9 signalosome, regulates the virulence in cryptococcus neoformans infection.the cop9 signalosome (csn) is a multisubunit protein complex, and it now has been found to participate in diverse cellular and developmental processes in various eukaryotic organisms. cryptococcus neoformans (c. neoformans) is an important basidiomycete pathogen that causes life-threatening meningoencephalitis primarily in the immune compromised population. here, we generated csn deletion mutants to investigate the role in cryptococcus infection. compared to other csn mutants, we identified a cs ...201627915049
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
unraveling fungal radiation resistance regulatory networks through the genome-wide transcriptome and genetic analyses of cryptococcus neoformans.the basidiomycetous fungus cryptococcus neoformans has been known to be highly radiation resistant and has been found in fatal radioactive environments such as the damaged nuclear reactor at chernobyl. to elucidate the mechanisms underlying the radiation resistance phenotype of c. neoformans, we identified genes affected by gamma radiation through genome-wide transcriptome analysis and characterized their functions. we found that genes involved in dna damage repair systems were upregulated in re ...201627899501
a monoclonal antibody to cryptococcus neoformans glucuronoxylomannan manifests hydrolytic activity for both peptides and polysaccharides.studies in the 1980s first showed that some natural antibodies were "catalytic" and able to hydrolyze peptide or phosphodiester bonds in antigens. many naturally occurring catalytic antibodies have since been isolated from human sera and associated with positive and negative outcomes in autoimmune disease and infection. the function and prevalence of these antibodies, however, remain unclear. a previous study suggested that the 18b7 monoclonal antibody against glucuronoxylomannan (gxm), the majo ...201727872188
rewiring of signaling networks modulating thermotolerance in the human pathogen cryptococcus neoformans.thermotolerance is a crucial virulence attribute for human pathogens, including the fungus cryptococcus neoformans that causes fatal meningitis in humans. loss of the protein kinase sch9 increases c. neoformans thermotolerance, but its regulatory mechanism has remained unknown. here, we studied the sch9-dependent and sch9-independent signaling networks modulating c. neoformans thermotolerance by using genome-wide transcriptome analysis and reverse genetic approaches. during temperature upshift, ...201727866167
erratum for voelz et al., cytokine signaling regulates the outcome of intracellular macrophage parasitism by cryptococcus neoformans. 201627864424
genomic epidemiology of cryptococcus yeasts identifies adaptation to environmental niches underpinning infection across an african hiv/aids cohort.emerging infections caused by fungi have become a widely recognized global phenomenon and are causing an increasing burden of disease. genomic techniques are providing new insights into the structure of fungal populations, revealing hitherto undescribed fine-scale adaptations to environments and hosts that govern their emergence as infections. cryptococcal meningitis is a neglected tropical disease that is responsible for a large proportion of aids-related deaths across africa; however, the ecol ...201627862555
high-resolution genetics identifies the lipid transfer protein sec14p as target for antifungal ergolines.invasive infections by fungal pathogens cause more deaths than malaria worldwide. we found the ergoline compound ngx04 in an antifungal screen, with selectivity over mammalian cells. high-resolution chemogenomics identified the lipid transfer protein sec14p as the target of ngx04 and compound-resistant mutations in sec14p define compound-target interactions in the substrate binding pocket of the protein. beyond its essential lipid transfer function in a variety of pathogenic fungi, sec14p is als ...201627855158
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
systemic approach to virulence gene network analysis for gaining new insight into cryptococcal virulence.cryptococcus neoformans is pathogenic yeast, responsible for highly lethal infections in compromised patients around the globe. c. neoformans typically initiates infections in mammalian lung tissue and subsequently disseminates to the central nervous system where it causes significant pathologies. virulence genes of c. neoformans are being characterized at an increasing rate, however, we are far from a comprehensive understanding of their roles and genetic interactions. some of these reported vi ...201627833589
invasive granulomatous cryptococcal sinusitis in an adult with multiple myeloma.we report a case of cryptococcal sinusitis, a rare presentation of cryptococcus neoformans infection in a patient with multiple myeloma. the objective of this case report is to highlight the utility of structural and functional imaging modalities in the differential diagnosis of sinonasal soft tissue masses in the immunocompromised patient population. pet-ct was the first imaging modality in this patient, who presented for routine follow-up staging of multiple myeloma, and was asymptomatic at th ...201727816878
using flow cytometry to analyze cryptococcus infection of macrophages.flow cytometry is a powerful analytical technique, which is increasingly being used to study the interaction between host cells and intracellular pathogens. flow cytometry is capable of measuring a greater number of infected cells within a sample compared to alternative techniques such as fluorescence microscopy. this means that robust quantification of rare events during infection is possible. our lab and others have developed flow cytometry methods to study interactions between host cells and ...201727815892
synergistic effect of pedalitin and amphotericin b against cryptococcus neoformans by in vitro and in vivo evaluation.cryptococcosis is an opportunistic fungal infection responsible for high morbidity and mortality in immunocompromised patients. combination of antifungal substances is a promising way to increase the percentage of successful treatment. pedalitin (ped) is a natural substance obtained from pterogyne nitens. the aim of this study was to verify the efficacy of ped alone and in combination with amphotericin b (amb) in vitro and in vivo against cryptococcus spp. in the in vitro assay, minimum inhibito ...201627742203
new weapons in the cryptococcus infection toolkit.the global burden of fungal infections is unacceptably high. the human fungal pathogen cryptococcus neoformans causes cryptococcosis and accounts for a significant proportion of this burden. cryptococci undergo a number of elaborate interactions with their hosts, including survival and proliferation within phagocytes as well as dissemination to the central nervous system and other tissues. in this review we highlight a number of exciting recent advances in the field of cryptococcal biology. in p ...201627522351
infections of the central nervous system after unrelated donor umbilical cord blood transplantation or human leukocyte antigen-matched sibling transplantation.we analyzed the incidence, clinical characteristics, prognostic factors, and outcome of central nervous system (cns) infections in consecutive patients with receiving umbilical cord blood transplantation (ucbt) (n = 343) or hla-matched sibling donor stem cell transplantation (mst) (n = 366). thirty-four cns infections were documented at a median time of 116 days after transplantation (range, 7 to 1161). the cumulative incidence (ci) risk of developing a cns infection was .6% at day +30, 2.3% at ...201727794456
environmental distribution of cryptococcus neoformans and c. gattii around the mediterranean basin. 201627789540
the putative autophagy regulator atg7 affects the physiology and pathogenic mechanisms of cryptococcus neoformans.we investigated the involvement of the autophagy protein 7 (atg7) in physiology and pathogenic potential of cryptococcus neoformans.201627750454
antifungal activity of eicosanoic acids isolated from the endophytic fungus mycosphaerella sp. against cryptococcus neoformans and c. gattii.the antifungal effects of two eicosanoic acids, 2-amino-3,4-dihydroxy-2-25-(hydroxymethyl)-14-oxo-6,12-eicosenoic acid (compound 1) and myriocin (compound 2), isolated from mycosphaerella sp. were evaluated against cryptococcus neoformans and c. gattii. the compounds displayed antifungal activities against several isolates of c. neoformans and c. gattii, with minimal inhibitory concentration (mic) values ranging from 0.49 to 7.82 μm for compound 1 and 0.48-1.95 μm for compound 2. in the checkerb ...201627693577
molecular characterization of adenylyl cyclase complex proteins using versatile protein-tagging plasmid systems in cryptococcus neoformans.in this study, we aimed to generate a series of versatile tagging plasmids that can be used in diverse molecular biological studies of the fungal pathogen cryptococcus neoformans. we constructed 12 plasmids that can be used to tag a protein of interest with a gfp, mcherry, 4×flag, or 6×ha, along with nourseothricin-, neomycin-, or hygromycin-resistant selection markers. using this tagging plasmid set, we explored the adenylyl cyclase complex (acc), consisting of adenylyl cyclase (cac1) and its a ...201727780958
inhibition of the calcineurin pathway by two flavonoids isolated from miliusa sinensis finet & gagnep.in order to discover plant-derived signaling pathway inhibitors with antifungal properties, a two-component screening system utilizing the calcineurin and hog1 mitogen-activated protein kinase pathways responsible for the virulence networks of cryptococcus neoformans was employed, owing to the counter-regulatory actions of these pathways. of the 1,000 plant extracts tested, two bioactive compounds from miliusa sinensis were found to act specifically on the calcineurin pathway of c. neoformans. t ...201627363478
cryptococcosis mimicking lung carcinoma with brain metastases in an immunocompetent patient.cryptococcosis is a fungal infection caused by cryptococcus spp. that enters the body via inhalation. this ubiquitous yeast has gained notoriety as an opportunistic pathogen in the immunosuppressed population. the authors report a case of a previously-well adult male presented with left-sided weakness. imaging demonstrated a pulmonary mass and 2 contrast-enhancing intracranial lesions-all features suggestive of a primary lung carcinoma with brain metastases. however, further investigations confi ...201727769644
cryptococcal cellulitis in a heart transplant recipient. 201627766302
identification and characterization of vni/vnii and novel vnii/vniv hybrids and impact of hybridization on virulence and antifungal susceptibility within the c. neoformans/c. gattii species complex.cryptococcus neoformans and c. gattii are pathogenic basidiomycetous yeasts and the commonest cause of fungal infection of the central nervous system. cryptococci are typically haploid but several inter-species, inter-varietal and intra-varietal hybrids have been reported. it has a bipolar mating system with sexual reproduction occurring normally between two individuals with opposite mating types, α and a. this study set out to characterize hybrid isolates within the c. neoformans/c. gattii spec ...201627764108
mode of action of a designed antimicrobial peptide: high potency against cryptococcus neoformans.there is a significant need for developing compounds that kill cryptococcus neoformans, the fungal pathogen that causes meningoencephalitis in immunocompromised individuals. here, we report the mode of action of a designed antifungal peptide, vg16krkp (vargwkrkcplfgkgg) against c. neoformans. it is shown that vg16krkp kills fungal cells mainly through membrane compromise leading to efflux of ions and cell metabolites. intracellular localization, inhibition of in vitro transcription, and dna bind ...201627760359
disruption of de novo adenosine triphosphate (atp) biosynthesis abolishes virulence in cryptococcus neoformans.opportunistic fungal pathogens such as cryptococcus neoformans are a growing cause of morbidity and mortality among immunocompromised populations worldwide. to address the current paucity of antifungal therapeutic agents, further research into fungal-specific drug targets is required. adenylosuccinate synthetase (adss) is a crucial enzyme in the adeosine triphosphate (atp) biosynthetic pathway, catalyzing the formation of adenylosuccinate from inosine monophosphate and aspartate. we have investi ...201627759389
distribution and association between environmental and clinical isolates of cryptococcus neoformans in bogotá-colombia, 2012-2015.the propagules of the fungal species cryptococcus neoformans and c. gattii, whose varieties are distributed world wide, are the primary cause of cryptococcosis, a life threatening disease. the study of environmental and clinical isolates of cryptococcosis is an important contribution to the epidemiology and ecology of the fungus. the aim of this work was to determine the presence of c. neoformans and c. gattii in the environment in bogotá, colombia's capital city and to establish the relation be ...201627706379
cryptococcal osteomyelitis of the skull in a liver transplant patient.cryptococcus neoformans is an opportunistic fungal pathogen and an important cause of morbidity and mortality in immunocompromised patients. we report a case of osteomyelitis caused by c. neoformans in a liver transplant recipient who presented with a headache and scalp lump after sustaining mild head trauma. there was no evidence of central nervous system involvement or dissemination. this is the first known case report of isolated cryptococcal osteomyelitis in a liver transplant recipient.201627601128
targeted genome editing via crispr in the pathogen cryptococcus neoformans.low rates of homologous integration have hindered molecular genetic studies in cryptococcus neoformans over the past 20 years, and new tools that facilitate genome manipulation in this important pathogen are greatly needed. to this end, we have investigated the use of a class 2 crispr system in c. neoformans (formerly c. neoformans var. grubii). we first expressed a derivative of the streptococcus pyogenes cas9 nuclease in c. neoformans, and showed that it has no effect on growth, production of ...201627711143
pulmonary cryptococcosis in the immunocompetent patient-many questions, some answers.background.  there are no prospective data regarding the management of pulmonary cryptococcosis in the immunocompetent patient. clinical guidelines recommend oral fluconazole for patients with mild to moderate symptoms and amphotericin b plus flucytosine followed by fluconazole for severe disease. it is unclear whether patients who have histological evidence of cryptococcus neoformans but negative cultures will even respond to drug treatment. we evaluated and managed a patient whose presentation ...201627704021
erratum to: transcriptional control of sexual development in cryptococcus neoformans. 201627687233
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