Publications

TitleAbstractYear(sorted descending)
Filter
PMID
Filter
highly efficient transformation system for malassezia furfur and malassezia pachydermatis using agrobacterium tumefaciens-mediated transformation.malassezia spp. are part of the normal human and animal mycobiota but are also associated with a variety of dermatological diseases. the absence of a transformation system hampered studies to reveal mechanisms underlying the switch from the non-pathogenic to pathogenic life style. here we describe, a highly efficient agrobacterium-mediated genetic transformation system for malassezia furfur and m. pachydermatis. a binary t-dna vector with the hygromycin b phosphotransferase (hpt) selection marke ...201728064034
nimesulide inhibits pathogenic fungi: pge2-dependent mechanisms.certain non-steroidal anti-inflammatory drugs can inhibit fungal growth, fungal prostaglandin e2 production, and enzyme activation. this study aims to investigate the antifungal effect of nimesulide against pathogenic filamentous fungi and yeast. the experiments detailed below were also designed to investigate whether the action is dependent on e2 fungal prostaglandins. our data showed that nimesulide exhibited potent antifungal activity, mainly against trichophyton mentagrophytes (atcc 9533) an ...201727866353
central role of the trehalose biosynthesis pathway in the pathogenesis of human fungal infections: opportunities and challenges for therapeutic development.invasive fungal infections cause significant morbidity and mortality in part due to a limited antifungal drug arsenal. one therapeutic challenge faced by clinicians is the significant host toxicity associated with antifungal drugs. another challenge is the fungistatic mechanism of action of some drugs. consequently, the identification of fungus-specific drug targets essential for fitness in vivo remains a significant goal of medical mycology research. the trehalose biosynthetic pathway is found ...201728298477
in vitro and in vivo antifungal profile of a novel and long acting inhaled azole, pc945, on aspergillus fumigatus infection.the profile of pc945, a novel triazole antifungal, designed for administration via inhalation, has been assessed in a range of in vitro and in vivo studies. pc945 was characterized as a potent, tight-binding inhibitor of aspergillus fumigatus sterol 14α-demethylase (cyp51a and cyp51b) activity (ic50, 0.23 μm and 0.22 μm, respectively), with characteristic type ii azole binding spectra. against 96 clinically isolated a. fumigatus strains, the mic values of pc945 ranged from 0.032∼>8 μg/ml, whilst ...201728223388
iron acquisition in fungal pathogens of humans.the devastating infections that fungal pathogens cause in humans are underappreciated relative to viral, bacterial and parasitic diseases. in recent years, the contributions to virulence of reductive iron uptake, siderophore-mediated uptake and heme acquisition have been identified in the best studied and most life-threatening fungal pathogens: candida albicans, cryptococcus neoformans and aspergillus fumigatus. in particular, exciting new work illustrates the importance of iron acquisition from ...201728217776
ram1 gene, encoding a subunit of farnesyltransferase, contributes to growth, antifungal susceptibility to amphotericin b of aspergillus fumigatus. 201728159997
broad spectrum anti-infective properties of benzisothiazolones and the parallels in their anti-bacterial and anti-fungal effects.various mono- and bis-benzisothiazolone derivatives were synthesized and screened against different strains of bacteria and fungi in order to understand the effect of multiple electrophilic sulfur atoms and substitution pattern in the immediate vicinity of reactive sulfur. staphyllococcus aureus-atcc 7000699, mrsa and s. aureus-atcc 29213 (quality control strain) were more susceptible to this class of compounds, and the most potent derivative 1.15 had mic50 of 0.4μg/ml (cf. gentamicin=0.78μg/ml) ...201728159413
activity of a long-acting echinocandin (cd101) and seven comparator antifungal agents tested against a global collection of contemporary invasive fungal isolates in the sentry 2014 antifungal surveillance program.the activity of cd101 and comparator antifungal agents against 606 invasive fungal isolates collected worldwide during 2014 was evaluated using the clinical and laboratory standards institute (clsi) method. all candida albicans (n = 251), candida tropicalis (n = 51), candida krusei (n = 16), and candida dubliniensis (n = 11) isolates were inhibited by ≤0.12 μg/ml of cd101 and were susceptible or showed wild-type susceptibility to the other echinocandins tested. five c. glabrata isolates (n = 100 ...201728052853
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
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
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
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 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
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
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
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
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
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
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
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
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
equine pulmonary cryptococcosis: a comparative literature review and evaluation of fluconazole monotherapy.cryptococcus is the most common fungal respiratory pathogen in australian horses, manifesting primarily as pulmonary granulomas. disease severity at presentation is dependent on the athletic use of the horse. the diagnosis and estimation of disease severity are centred around clinical findings, cytological evaluation of respiratory tract secretions, diagnostic imaging, and antigen titre testing. both the lateral flow assay and the latex cryptococcal antigen titre are used, and important similari ...201727655152
pulsed dye laser treatment of primary cryptococcal laryngitis: a novel approach to an uncommon disease.an 82-year-old supplemental oxygen dependent woman with severe copd presented with an eight month history of worsening hoarseness and stridor. office laryngoscopy revealed laryngeal edema and ulcerative masses throughout the larynx. in-office biopsies were positive for cryptococcus neoformans. this report details a novel approach to the treatment of cryptococcal laryngitis, a combination of in-office pulsed-dye laser (pdl) ablation and medical therapy. despite treatment with oral fluconazole, th ...201727654751
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
endoscopic ultrasound fine-needle aspiration diagnosis of cryptococcus neoformans. 201727639329
molecular identification, antifungal resistance and virulence of cryptococcus neoformans and cryptococcus deneoformans isolated in seville, spain.cryptococcal meningitis is one of the leading causes of death in hiv/aids patients. our aim was to in order to characterise the epidemiology, antifungal susceptibility pattern and virulence of 28 cyptococcus sp. strains recovered from 12 aids patients during two years in a spanish single institution. antifungal susceptibility testing was performed according to the clsi protocols. clinical strains were molecularly characterised by serotyping, mating type, pcr fingerprinting (m13 and gaca4 microsa ...201727633849
cysteinyl leukotrienes as novel host factors facilitating cryptococcus neoformans penetration into the brain.cryptococcus neoformas infection of the central nervous system (cns) continues to be an important cause of mortality and morbidity, and a major contributing factor is our incomplete knowledge of the pathogenesis of this disease. here, we provide the first direct evidence that c. neoformans exploits host cysteinyl leukotrienes (lts), formed via lt biosynthetic pathways involving cytosolic phospholipase a2 α (cpla2 α) and 5-lipoxygenase (5-lo) and acting via cysteinyl leukotriene type 1 receptor ( ...201727573789
geographic distribution of patients affected by cryptococcus neoformans/cryptococcus gattii species complexes meningitis, pigeon and tree populations in southern brazil.cryptococcal meningitis is mainly caused by members of the c. neoformans/c. gattii species complexes. the ecological niches of cryptococcus species have extensively been studied, but its epidemiological relationship with meningitis cases is still unknown. in this study, we estimate the relationship between cryptococcal meningitis cases and tree and pigeon populations, the classical niches of members of c. neoformans/c. gattii sensu lato. we analysed the records of every patient whose cerebrospin ...201727561904
cryptococcus neoformans ugt1 encodes a udp-galactose/udp-galnac transporter.cryptococcus neoformans, an opportunistic fungal pathogen, produces a glycan capsule to evade the immune system during infection. this definitive virulence factor is composed mainly of complex polysaccharides, which are made in the secretory pathway by reactions that utilize activated nucleotide sugar precursors. although the pathways that synthesize these precursors are known, the identity and the regulation of the nucleotide sugar transporters (nsts) responsible for importing them into luminal ...201727496760
quercetin and rutin as potential agents antifungal against cryptococcus spp.amphotericin b is a fungicidal substance that is treatment of choice for most systemic fungal infections affecting as cryptococcosis the immunocompromised patients. however, severe side effects have limited the utility of this drug. the aim of this study was to evaluate the antifungal effect of the combination of amphotericin b with quercetin or rutin and as a protective of citotoxic effect. the antifungal activity to amphotericin b, quercetin and rutin alone and in combination was determined in ...201727166572
immune reconstitution syndrome in a human immunodeficiency virus infected child due to giardiasis leading to shock.human immunodeficiency virus (hiv)-associated immune reconstitution inflammatory syndrome has been reported in association with tuberculosis, herpes zoster (shingles), cryptococcus neoformans, kaposi's sarcoma, pneumocystis pneumonia, hepatitis b virus, hepatitis c virus, herpes simplex virus, histoplasma capsulatum, human papillomavirus, and cytomegalovirus. however, it has never been documented with giardiasis. we present a 7-year-old hiv infected girl who developed diarrhea and shock followin ...201726985424
antifungal amide alkaloids from the aerial parts of piper flaviflorum and piper sarmentosum.sixty-three amide alkaloids, including three new, piperflaviflorine a (1), piperflaviflorine b (2), and sarmentamide d (4), and two previously synthesized ones, (1e,3s)-1-cinnamoyl-3- hydroxypyrrolidine (3) and n-[7'-(4'-methoxyphenyl)ethyl]-2-methoxybenzamide (5), were isolated from the aerial parts of piper flaviflorum and piper sarmentosum. their structures were elucidated by detailed spectroscopic analysis and, in case of 3, by single-crystal x-ray diffraction. most of the isolates were test ...201727405106
relative contributions of prenylation and postprenylation processing in cryptococcus neoformans pathogenesis.prenyltransferase enzymes promote the membrane localization of their target proteins by directing the attachment of a hydrophobic lipid group at a conserved c-terminal caax motif. subsequently, the prenylated protein is further modified by postprenylation processing enzymes that cleave the terminal 3 amino acids and carboxymethylate the prenylated cysteine residue. many prenylated proteins, including ras1 and ras-like proteins, require this multistep membrane localization process in order to fun ...201727303728
the zinc finger protein mig1 regulates mitochondrial function and azole drug susceptibility in the pathogenic fungus cryptococcus neoformans.the opportunistic pathogen cryptococcus neoformans causes fungal meningoencephalitis in immunocompromised individuals. in previous studies, we found that the hap complex in this pathogen represses genes encoding mitochondrial respiratory functions and tricarboxylic acid (tca) cycle components under low-iron conditions. the orthologous hap2/3/4/5 complex in saccharomyces cerevisiae exerts a regulatory influence on mitochondrial functions, and hap4 is subject to glucose repression via the carbon c ...201727303693
antifungal efficacy of amphotericin b encapsulated fibrin microsphere for treating cryptococcus neoformans infection in swiss albino mice.a natural and biocompatible fibrin microsphere is one of the most promising dual delivery vehicle as compared to other traditionally designed delivery modalities. it represents sustained delivery of encapsulated drug and is easily biodegradable in the blood circulation. in the present study, we evaluated the systemic augmentation of the antifungal activity of amphotericin b loaded in fibrin microsphere (amb-fibrin microsphere) against cryptococcosis in swiss albino mice. mice infected with crypt ...201727294976
pathology of thyroid in acquired immunodeficiency syndrome.the course of human immunodeficiency virus infection and the acquired immunodeficiency syndrome can be complicated by a variety of endocrine abnormalities, including abnormalities of thyroid gland.201727510660
amino acid substitution in cryptococcus neoformans lanosterol 14-α-demethylase involved in fluconazole resistance in clinical isolates.the molecular basis of fluconazole resistance in cryptococcus neoformans has been poorly studied. a common azole resistance mechanism in candida species is the acquisition of point mutations in the erg11 gene encoding the enzyme lanosterol 14-α-demethylase, target of the azole class of drugs. in c. neoformans only two mutations were described in this gene. in order to evaluate other mutations that could be implicated in fluconazole resistance in c. neoformans we studied the genomic sequence of t ...201727311753
Refresh
firstprev
12345678910...
nextlast
Displaying items 1 - 100 of 7882