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https://www.readbyqxmd.com/read/28381925/molecular-insights-into-pathogenesis-and-infection-with-aspergillus-fumigatus
#1
REVIEW
Ciamak Ghazaei
The virulence of fungi is dependent on multiple factors, including the immune status of patients and biological features of fungi. In particular, the virulence of Aspergillus fumigatus is due to the complex interaction among various molecules involved in thermotolerance (such as ribosomal biogenesis proteins, α-mannosyltransferase and heat shock proteins), pigment production (DHN-melanin), immune evasion (like melanin and hydrophobin) and nutrient uptake (such as siderophores and zinc transporters). Other molecules also play important roles in the virulence of A...
March 2017: Malaysian Journal of Medical Sciences: MJMS
https://www.readbyqxmd.com/read/28376389/identification-and-characterization-of-the-verticillin-biosynthetic-gene-cluster-in-clonostachys-rogersoniana
#2
Ying Wang, Pengjie Hu, Yuanyuan Pan, Yaxin Zhu, Xingzhong Liu, Yongsheng Che, Gang Liu
Verticillin is one of the dimeric epipolythiodioxopiperazines (ETPs) which are toxic secondary metabolites produced only by fungi. ETPs have received substantial attention since its complex molecular architecture and a wide range of biological activities. Although biosynthesis of the monomeric gliotoxin has been studied extensively, the biosynthetic pathway of dimeric ETPs is far from being studied. To investigate the biosynthesis of dimeric ETPs and expand our understanding of their dimerization, the verticillin biosynthetic gene cluster (ver) was identified and cloned from a genomic DNA fosmid library of the Cordyceps-colonizing fungus Clonostachys rogersoniana with the designed primers based on the sequence of a nonribosomal peptide synthetase (NRPS) ChaP which was predicted to be responsible for chaetocin biosynthesis in Chaetomium virescens...
April 1, 2017: Fungal Genetics and Biology: FG & B
https://www.readbyqxmd.com/read/28301237/aspergillosis-a-natural-infection-in-poultry-mycological-and-molecular-characterization-and-determination-of-gliotoxin-in-aspergillus-fumigatus-isolates
#3
Verónica Montes de Oca, Sara Esther Valdés, Carolina Segundo, Gabriela Guadalupe Gómez, José Ramírez, Roberto Arnulfo Cervantes
Aspergillosis affects all types of birds; it causes the loss of specimens with high ecologic value and also leads to significant economic losses within the poultry industry. The main etiologic agent is Aspergillus fumigatus , a filamentary fungus with multiple virulence factors, such as gliotoxin (GT), which is an immunosuppressive epipolythiodioxopiperazine molecule. Necropsy was performed on 73 poultry from different provenances, all of which presented with a respiratory semiology compatible with aspergillosis...
March 2017: Avian Diseases
https://www.readbyqxmd.com/read/28280460/androstenediol-reduces-demyelination-induced-axonopathy-in-the-rat-corpus-callosum-impact-on-microglial-polarization
#4
Samah Kalakh, Abdeslam Mouihate
Aims: We have previously shown that the neurosteroid androstenediol (ADIOL) promotes remyelination following gliotoxin-induced demyelination. However, the impact of this ADIOL on axonal recovery is not yet known. In the present study, we investigated the impact of ADIOL on axonal integrity following a focal demyelination in the corpus callosum. Methods: A 2 μl solution of either ethidium bromide (EB; 0.04%) or pyrogen-free saline were stereotaxically injected into the corpus callosum of Sprague Dawley rats...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28276430/beta-trace-protein-as-a-new-non-invasive-immunological-marker-for-quinolinic-acid-induced-impaired-blood-brain-barrier-integrity
#5
Andreas Baranyi, Omid Amouzadeh-Ghadikolai, Dirk von Lewinski, Robert J Breitenecker, Tatjana Stojakovic, Winfried März, Christoph Robier, Hans-Bernd Rothenhäusler, Harald Mangge, Andreas Meinitzer
Quinolinic acid, a macrophage/microglia-derived excitotoxin fulfills a plethora of functions such as neurotoxin, gliotoxin, and proinflammatory mediator, and it alters the integrity and cohesion of the blood-brain barrier in several pathophysiological states. Beta-trace protein (BTP), a monomeric glycoprotein, is known to indicate cerebrospinal fluid leakage. Thus, the prior aim of this study was to investigate whether BTP might non-invasively indicate quinolinic acid-induced impaired blood-brain barrier integrity...
March 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28213885/epigenetic-modifier-induced-enhancement-of-fumiquinazoline-c-production-in-aspergillus-fumigatus-ga-l7-an-endophytic-fungus-from-grewia-asiatica-l
#6
Ankita Magotra, Manjeet Kumar, Manoj Kushwaha, Praveen Awasthi, Chand Raina, Ajai Prakash Gupta, Bhahwal A Shah, Sumit G Gandhi, Asha Chaubey
Present study relates to the effect of valproic acid, an epigenetic modifier on the metabolic profile of Aspergillus fumigatus (GA-L7), an endophytic fungus isolated from Grewia asiatica L. Seven secondary metabolites were isolated from A. fumigatus (GA-L7) which were identified as: pseurotin A, pseurotin D, pseurotin F2, fumagillin, tryprostatin C, gliotoxin and bis(methylthio)gliotoxin. Addition of valproic acid in the growth medium resulted in the alteration of secondary metabolic profile with an enhanced production of a metabolite, fumiquinazoline C by tenfolds...
December 2017: AMB Express
https://www.readbyqxmd.com/read/28179499/structural-mechanistic-and-functional-insight-into-gliotoxin-bis-thiomethylation-in-aspergillus-fumigatus
#7
Stephen K Dolan, Tobias Bock, Vanessa Hering, Rebecca A Owens, Gary W Jones, Wulf Blankenfeldt, Sean Doyle
Gliotoxin is an epipolythiodioxopiperazine (ETP) class toxin, contains a disulfide bridge that mediates its toxic effects via redox cycling and is produced by the opportunistic fungal pathogen Aspergillus fumigatus Self-resistance against gliotoxin is effected by the gliotoxin oxidase GliT, and attenuation of gliotoxin biosynthesis is catalysed by gliotoxin S-methyltransferase GtmA. Here we describe the X-ray crystal structures of GtmA-apo (1.66 Å), GtmA complexed to S-adenosylhomocysteine (1.33 Å) and GtmA complexed to S-adenosylmethionine (2...
February 2017: Open Biology
https://www.readbyqxmd.com/read/28149676/genomic-insight-into-pathogenicity-of-dematiaceous-fungus-corynespora-cassiicola
#8
Hong Keat Looi, Yue Fen Toh, Su Mei Yew, Shiang Ling Na, Yung-Chie Tan, Pei-Sin Chong, Jia-Shiun Khoo, Wai-Yan Yee, Kee Peng Ng, Chee Sian Kuan
Corynespora cassiicola is a common plant pathogen that causes leaf spot disease in a broad range of crop, and it heavily affect rubber trees in Malaysia (Hsueh, 2011; Nghia et al., 2008). The isolation of UM 591 from a patient's contact lens indicates the pathogenic potential of this dematiaceous fungus in human. However, the underlying factors that contribute to the opportunistic cross-infection have not been fully studied. We employed genome sequencing and gene homology annotations in attempt to identify these factors in UM 591 using data obtained from publicly available bioinformatics databases...
2017: PeerJ
https://www.readbyqxmd.com/read/28068839/antituberculosis-compounds-from-a-deep-sea-derived-fungus-aspergillus-sp-scsio-ind09f01
#9
Xiaowei Luo, Xuefeng Zhou, Xiuping Lin, Xiaochu Qin, Tianyu Zhang, Junfeng Wang, Zhengchao Tu, Bin Yang, Shengrong Liao, Yongqi Tian, Xiaoyan Pang, Kumaravel Kaliyaperumal, Jian Lin Li, Huaming Tao, Yonghong Liu
Eleven diketopiperazine and fumiquinazoline alkaloids (1-11) together with a tetracyclic triterpenoid helvolic acid (12) were obtained from the cultures of a deep-sea derived fungus Aspergillus sp. SCSIO Ind09F01. The structures of these compounds (1-12) were determined mainly by the extensive NMR, ESIMS spectra data and by comparison with previously described compounds. Besides, anti-tuberculosis, cytotoxic, antibacterial, COX-2 inhibitory and antiviral activities of these compounds were evaluated. Gliotoxin (3), 12,13-dihydroxy-fumitremorgin C (11) and helvolic acid (12) exhibited very strong anti-tuberculosis activity towards Mycobacterium tuberculosis with the prominent MIC50 values of <0...
January 9, 2017: Natural Product Research
https://www.readbyqxmd.com/read/27975125/antidepressant-like-activity-of-the-neuropeptide-y-y5-receptor-antagonist-lu-aa33810-behavioral-molecular-and-immunohistochemical-evidence
#10
Helena Domin, Bernadeta Szewczyk, Bartłomiej Pochwat, Monika Woźniak, Maria Śmiałowska
RATIONALE: It has recently been found that chronic treatment with the highly selective, brain-penetrating Y5 receptor antagonist, Lu AA33810 [N-[[trans-4-[(4,5-dihydro [1] benzothiepino[5,4-d] thiazol-2-yl) amino] cyclohexyl]methyl]-methanesulfonamide], produces antidepressant-like effects in the rat chronic mild stress model. OBJECTIVE: In the present study, we investigated the possible antidepressant-like activity of Lu AA33810 in rats subjected to glial ablation in the prefrontal cortex (PFC) by the gliotoxin L-AAA, which is an astroglial degeneration model of depression...
February 2017: Psychopharmacology
https://www.readbyqxmd.com/read/27939578/disseminated-aspergillosis-in-an-immunocompetent-patient-with-detectable-bis-methylthio-gliotoxin-and-negative-galactomannan
#11
Matxalen Vidal-García, Pilar Sáncehez-Chueca, María Pilar Domingo, Carlos Ballester, Lourdes Roc, Isabel Ferrer, María José Revillo, Julián Pardo, Eva María Gálvez, Antonio Rezusta
BACKGROUND: Disseminated invasive aspergillosis is an exceptional finding in immunocompetent hosts. As in immunocompromised patients, it has high mortality rates. Early diagnostic methods are required in order to properly manage the patient. Bis(methylthio)gliotoxin (bmGT) is a novel biomarker, useful in onco-hematological patients. CASE REPORT: A 70-year-old male, with non-insulin dependent type II diabetes mellitus and a past surgery history of aortic valve replacement with coronary by-pass five years ago, was seen in the emergency department with blurred vision...
December 8, 2016: Revista Iberoamericana de Micología
https://www.readbyqxmd.com/read/27748436/ergothioneine-biosynthesis-and-functionality-in-the-opportunistic-fungal-pathogen-aspergillus-fumigatus
#12
Kevin J Sheridan, Beatrix Elisabeth Lechner, Grainne O' Keeffe, Markus A Keller, Ernst R Werner, Herbert Lindner, Gary W Jones, Hubertus Haas, Sean Doyle
Ergothioneine (EGT; 2-mercaptohistidine trimethylbetaine) is a trimethylated and sulphurised histidine derivative which exhibits antioxidant properties. Here we report that deletion of Aspergillus fumigatus egtA (AFUA_2G15650), which encodes a trimodular enzyme, abrogated EGT biosynthesis in this opportunistic pathogen. EGT biosynthetic deficiency in A. fumigatus significantly reduced resistance to elevated H2O2 and menadione, respectively, impaired gliotoxin production and resulted in attenuated conidiation...
October 17, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27649508/scf-ubiquitin-ligase-f-box-protein-fbx15-controls-nuclear-co-repressor-localization-stress-response-and-virulence-of-the-human-pathogen-aspergillus-fumigatus
#13
Bastian Jöhnk, Özgür Bayram, Anja Abelmann, Thorsten Heinekamp, Derek J Mattern, Axel A Brakhage, Ilse D Jacobsen, Oliver Valerius, Gerhard H Braus
F-box proteins share the F-box domain to connect substrates of E3 SCF ubiquitin RING ligases through the adaptor Skp1/A to Cul1/A scaffolds. F-box protein Fbx15 is part of the general stress response of the human pathogenic mold Aspergillus fumigatus. Oxidative stress induces a transient peak of fbx15 expression, resulting in 3x elevated Fbx15 protein levels. During non-stress conditions Fbx15 is phosphorylated and F-box mediated interaction with SkpA preferentially happens in smaller subpopulations in the cytoplasm...
September 2016: PLoS Pathogens
https://www.readbyqxmd.com/read/27584150/characterization-of-gprk-encoding-a-putative-hybrid-g-protein-coupled-receptor-in-aspergillus-fumigatus
#14
Mun-Gu Jung, Sung Su Kim, Jae-Hyuk Yu, Kwang-Soo Shin
The G-protein-coupled receptor (GPCR) family represents the largest and most varied collection of membrane embedded proteins that are sensitized by ligand binding and interact with heterotrimeric G proteins. Despite their presumed critical roles in fungal biology, the functions of the GPCR family members in the opportunistic human pathogen Aspergillus fumigatus are largely unknown, as only two (GprC and GprD) of the 15 predicted GPCRs have been studied. Here, we characterize the gprK gene, which is predicted to encode a hybrid GPCR with both 7-transmembrane and regulator of G-protein signaling (RGS) domains...
2016: PloS One
https://www.readbyqxmd.com/read/27106236/the-fungal-metabolite-gliotoxin-inhibits-proteasome-proteolytic-activity-and-induces-an-irreversible-pseudocystic-transformation-and-cell-death-in-tritrichomonas-foetus
#15
Antonio Pereira-Neves, Rubem F S Menna-Barreto, Marlene Benchimol
Proteasomal proteolysis is required for a wide range of cellular processes, including protein quality control, cell cycle progression, cell death and metabolic adaptation to environment changes or stress responses. Proteasome inhibitors are useful compounds for determining the roles of proteasome in eukaryotic cells. Here, we investigated the effects of gliotoxin, a proteasome inhibitor, on the cell growth, replication, ultrastructure, DNA integrity and proteasomal proteolytic activity of the protist parasite Tritrichomonas foetus...
August 2016: Parasitology Research
https://www.readbyqxmd.com/read/27062641/l-lactate-mediates-neuroprotection-against-ischaemia-by-increasing-trek1-channel-expression-in-rat-hippocampal-astrocytes-in%C3%A2-vitro
#16
Aditi Banerjee, Swagata Ghatak, Sujit Kumar Sikdar
Brain ischaemia is a highly debilitating condition where shortage of oxygen and glucose leads to profuse cell death. Lactate is a neuroprotective metabolite whose concentrations increase up to 15-30 mmol/L during ischaemia and TREK1 is a neuroprotective potassium channel which is upregulated during ischaemia. The aim of this study was to investigate the effect of l-lactate on TREK1 expression and to evaluate the role of l-lactate-TREK1 interaction in conferring neuroprotection in ischaemia-prone hippocampus...
July 2016: Journal of Neurochemistry
https://www.readbyqxmd.com/read/27048806/gliotoxin-suppresses-macrophage-immune-function-by-subverting-phosphatidylinositol-3-4-5-trisphosphate-homeostasis
#17
Daniel Schlam, Johnathan Canton, Marvin Carreño, Hannah Kopinski, Spencer A Freeman, Sergio Grinstein, Gregory D Fairn
UNLABELLED: Aspergillus fumigatus, an opportunistic fungal pathogen, spreads in the environment by releasing numerous conidia that are capable of reaching the small alveolar airways of mammalian hosts. In otherwise healthy individuals, macrophages are responsible for rapidly phagocytosing and eliminating these conidia, effectively curbing their germination and consequent invasion of pulmonary tissue. However, under some circumstances, the fungus evades phagocyte-mediated immunity and persists in the respiratory tree...
April 5, 2016: MBio
https://www.readbyqxmd.com/read/26808594/sequential-inactivation-of-gliotoxin-by-the-s-methyltransferase-tmta
#18
Elke R Duell, Manuel Glaser, Camille Le Chapelain, Iris Antes, Michael Groll, Eva M Huber
The epipolythiodioxopiperazine (ETP) gliotoxin mediates toxicity via its reactive thiol groups and thereby contributes to virulence of the human pathogenic fungus Aspergillus fumigatus. Self-intoxication of the mold is prevented either by reversible oxidation of reduced gliotoxin or by irreversible conversion to bis(methylthio)gliotoxin. The latter is produced by the S-methyltransferase TmtA and attenuates ETP biosynthesis. Here, we report the crystal structure of TmtA in complex with S-(5'-adenosyl)-l-homocysteine...
April 15, 2016: ACS Chemical Biology
https://www.readbyqxmd.com/read/26779142/extrolites-of-aspergillus-fumigatus-and-other-pathogenic-species-in-aspergillus-section-fumigati
#19
REVIEW
Jens C Frisvad, Thomas O Larsen
Aspergillus fumigatus is an important opportunistic human pathogen known for its production of a large array of extrolites. Up to 63 species have been described in Aspergillus section Fumigati, some of which have also been reliably reported to be pathogenic, including A. felis, A. fischeri, A. fumigatiaffinis, A. fumisynnematus, A. hiratsukae, A. laciniosus, A. lentulus, A. novofumigatus, A. parafelis, A. pseudofelis, A. pseudoviridinutans, A. spinosus, A. thermomutatus, and A. udagawae. These species share the production of hydrophobins, melanins, and siderophores and ability to grow well at 37°C, but they only share some small molecule extrolites, that could be important factors in pathogenicity...
2015: Frontiers in Microbiology
https://www.readbyqxmd.com/read/26678078/clinical-validity-of-bis-methylthio-gliotoxin-for-the-diagnosis-of-invasive-aspergillosis
#20
Matxalen Vidal-García, M Pilar Domingo, Beatriz De Rueda, Lourdes Roc, M Pilar Delgado, M José Revillo, Julián Pardo, Eva M Gálvez, Antonio Rezusta
Early and accurate diagnosis of invasive aspergillosis (IA) is one of the most critical steps needed to efficiently treat the infection and reduce the high mortality rates that can occur. We have previously found that the Aspergillus spp. secondary metabolite, bis(methylthio)gliotoxin (bmGT), can be detected in the serum from patients with possible/probable IA. Thus, it could be used as a diagnosis marker of the infection. However, there is no data available concerning the sensitivity, specificity and performance of bmGT to detect the infection...
March 2016: Applied Microbiology and Biotechnology
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