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'Aspergillus' and 'virulence'

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https://www.readbyqxmd.com/read/28737735/the-putative-histone-methyltransferase-dot1-regulates-aflatoxin-and-pathogenicity-attributes-in-aspergillus-flavus
#1
Linlin Liang, Yinghang Liu, Kunlong Yang, Guinan Lin, Zhangling Xu, Huahui Lan, Xiuna Wang, Shihua Wang
Lysine methyltransferases transfer methyl groups in specific lysine sites, which regulates a variety of important biological processes in eukaryotes. In this study, we characterized a novel homolog of the yeast methyltransferase DOT1 in A. flavus, and observed the roles of dot1 in A. flavus. Deletion of dot1 showed a significant decrease in conidiation, but an increase in sclerotia formation. A change in viability to multiple stresses was also found in the Δdot1 mutant. Additionally, aflatoxin (AF) production was found severely impaired in the Δdot1 mutant...
July 24, 2017: Toxins
https://www.readbyqxmd.com/read/28720735/a-nonredundant-phosphopantetheinyl-transferase-ppta-is-a-novel-antifungal-target-that-directs-secondary-metabolite-siderophore-and-lysine-biosynthesis-in-aspergillus-fumigatus-and-is-critical-for-pathogenicity
#2
Anna Johns, Daniel H Scharf, Fabio Gsaller, Hella Schmidt, Thorsten Heinekamp, Maria Straßburger, Jason D Oliver, Mike Birch, Nicola Beckmann, Katharine S Dobb, Jane Gilsenan, Bharatkumar Rash, Elaine Bignell, Axel A Brakhage, Michael J Bromley
Secondary metabolites are key mediators of virulence for many pathogens. Aspergillus fumigatus produces a vast array of these bioactive molecules, the biosynthesis of which is catalyzed by nonribosomal peptide synthetases (NRPSs) or polyketide synthases (PKSs). Both NRPSs and PKSs harbor carrier domains that are primed for acceptance of secondary metabolic building blocks by a phosphopantetheinyl transferase (P-pant). The A. fumigatus P-pant PptA has been shown to prime the putative NRPS Pes1 in vitro and has an independent role in lysine biosynthesis; however, its role in global secondary metabolism and its impact on virulence has not been described...
July 18, 2017: MBio
https://www.readbyqxmd.com/read/28716113/whole-metagenome-profiles-of-particulates-collected-from-the-international-space-station
#3
Nicholas A Be, Aram Avila-Herrera, Jonathan E Allen, Nitin Singh, Aleksandra Checinska Sielaff, Crystal Jaing, Kasthuri Venkateswaran
BACKGROUND: The built environment of the International Space Station (ISS) is a highly specialized space in terms of both physical characteristics and habitation requirements. It is unique with respect to conditions of microgravity, exposure to space radiation, and increased carbon dioxide concentrations. Additionally, astronauts inhabit a large proportion of this environment. The microbial composition of ISS particulates has been reported; however, its functional genomics, which are pertinent due to potential impact of its constituents on human health and operational mission success, are not yet characterized...
July 17, 2017: Microbiome
https://www.readbyqxmd.com/read/28701066/the-cell-wall-of-the-human-fungal-pathogen-aspergillus-fumigatus-biosynthesis-organization-immune-response-and-virulence
#4
Jean-Paul Latgé, Anne Beauvais, Georgios Chamilos
More than 90% of the cell wall of the filamentous fungus Aspergillus fumigatus comprises polysaccharides. Biosynthesis of the cell wall polysaccharides is under the control of three types of enzymes: transmembrane synthases, which are anchored to the plasma membrane and use nucleotide sugars as substrates, and cell wall-associated transglycosidases and glycosyl hydrolases, which are responsible for remodeling the de novo synthesized polysaccharides and establishing the three-dimensional structure of the cell wall...
July 12, 2017: Annual Review of Microbiology
https://www.readbyqxmd.com/read/28694801/the-gata-type-transcription-factor-csm1-regulates-conidiation-and-secondary-metabolism-in-fusarium-fujikuroi
#5
Eva-Maria Niehaus, Julia Schumacher, Immo Burkhardt, Patrick Rabe, Eduard Spitzer, Martin Münsterkötter, Ulrich Güldener, Christian M K Sieber, Jeroen S Dickschat, Bettina Tudzynski
GATA-type transcription factors (TFs) such as the nitrogen regulators AreA and AreB, or the light-responsive TFs WC-1 and WC-2, play global roles in fungal growth and development. The conserved GATA TF NsdD is known as an activator of sexual development and key repressor of conidiation in Aspergillus nidulans, and as light-regulated repressor of macroconidia formation in Botrytis cinerea. In the present study, we functionally characterized the NsdD ortholog in Fusarium fujikuroi, named Csm1. Deletion of this gene resulted in elevated microconidia formation in the wild-type (WT) and restoration of conidiation in the non-sporulating velvet mutant Δvel1 demonstrating that Csm1 also plays a role as repressor of conidiation in F...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28677124/myba-a-transcription-factor-involved-in-conidiation-and-conidial-viability-of-the-human-pathogen-aspergillus-fumigatus
#6
Isabel Valsecchi, Özlem Sarikaya Bayram, Joanne Wong Sak Hoi, Laetitia Muszkieta, John Gibbons, Marie-Christine Prevost, Adeline Mallet, Jacomina Krijnse-Locker, Oumaima Ibrahim-Granet, Isabelle Mouyna, Paul Carr, Michael Bromley, VishuKumar Aimanianda, Y Jae-Hyuk Yu, Antonis Rokas, Gerhard Braus, Cosmin Saveanu, Özgür Bayram, Jean Paul Latgé
Aspergillus fumigatus, a ubiquitous human fungal pathogen, produces asexual spores (conidia), which are the main mode of propagation, survival, and infection of this human pathogen. In this study, we present the molecular characterization of a novel regulator of conidiogenesis and conidial survival called MybA because the predicted protein contains a Myb DNA binding motif. Cellular localisation of the MybA::Gfp fusion and immunoprecipitation of the MybA::Gfp or MybA::3xHa protein showed that MybA is localised to the nucleus...
July 5, 2017: Molecular Microbiology
https://www.readbyqxmd.com/read/28658594/targeting-protein-localization-for-anti-infective-therapy
#7
J Andrew Alspaugh
Invasive fungal infections are devastating complications of immunocompromised patients. These infections are notoriously difficult to treat given the surprising degree of physiological similarity between fungi and the infected mammalian host. To explore novel targets for antifungal therapy, investigators have studied enzymes involved in the post-translational modification of highly conserved signaling proteins such as the Ras-like GTPases. These modifications are often required for protein localization and function...
June 28, 2017: Virulence
https://www.readbyqxmd.com/read/28652019/sphingolipids-from-the-human-fungal-pathogen-aspergillus-fumigatus
#8
REVIEW
Thierry Fontaine
Sphingolipids (SPLs) are key components of the plasma membrane in yeast and filamentous fungi. These molecules are involved in a number of cellular processes, and particularly, SGLs are essential components of the highly polarized fungal growth where they are required for the formation of the polarisome organization at the hyphal apex. Aspergillus fumigatus, a human fungal pathogen, produce SGLs that are discriminated into neutral cerebrosides, glycosylinositolphosphoceramides (GIPCs) and glycosylphosphatidylinositol (GPI) anchors...
June 23, 2017: Biochimie
https://www.readbyqxmd.com/read/28647921/proteome-profile-of-aspergillus-terreus-conidia-at-germinating-stage-identification-of-probable-virulent-factors-and-enzymes-from-mycotoxin-pathways
#9
Raman Thakur, Jata Shankar
Aspergillus terreus is an emerging opportunistic fungal pathogen that causes invasive aspergillosis in immunocompromised individuals. The main risk group of individuals for this organism is leukopenic patients, individuals having cancers, bone marrow transplant persons and those who have immunological disorders. The lack of early diagnostic marker for A. terreus and intrinsic resistance to Amphotericin B, further limits the successful therapy of A. terreus-associated infections. The germination of inhaled conidia is the key step to establish successful invasion in host tissues or organs...
June 24, 2017: Mycopathologia
https://www.readbyqxmd.com/read/28634301/microbial-glycoside-hydrolases-as-antibiofilm-agents-with-cross-kingdom-activity
#10
Brendan D Snarr, Perrin Baker, Natalie C Bamford, Yukiko Sato, Hong Liu, Mélanie Lehoux, Fabrice N Gravelat, Hanna Ostapska, Shane R Baistrocchi, Robert P Cerone, Elan E Filler, Matthew R Parsek, Scott G Filler, P Lynne Howell, Donald C Sheppard
Galactosaminogalactan and Pel are cationic heteropolysaccharides produced by the opportunistic pathogens Aspergillus fumigatus and Pseudomonas aeruginosa, respectively. These exopolysaccharides both contain 1,4-linked N-acetyl-d-galactosamine and play an important role in biofilm formation by these organisms. Proteins containing glycoside hydrolase domains have recently been identified within the biosynthetic pathway of each exopolysaccharide. Recombinant hydrolase domains from these proteins (Sph3h from A...
July 3, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28622385/effect-of-acute-predation-with-bacteriophage-on-intermicrobial-aggression-by-pseudomonas-aeruginosa
#11
Patrick R Secor, Gabriele Sass, Hasan Nazik, David A Stevens
In persons with structural lung disease, particularly those with cystic fibrosis (CF), chronic airway infections cause progressive loss of lung function. CF airways can be colonized by a variety of microorganisms; the most frequently encountered bacterial and fungal pathogens are Pseudomonas aeruginosa and Aspergillus fumigatus, respectively. Co-infection with P. aeruginosa and A. fumigatus often results in a more rapid loss of lung function, indicating that interactions between these pathogens affect infection pathogenesis...
2017: PloS One
https://www.readbyqxmd.com/read/28622118/imaging-spectrum-of-invasive-fungal-and-fungal-like-infections
#12
Hilary L P Orlowski, Sebastian McWilliams, Vincent M Mellnick, Sanjeev Bhalla, Meghan G Lubner, Perry J Pickhardt, Christine O Menias
Invasive fungal and fungal-like infections contribute to substantial morbidity and mortality in immunocompromised individuals. The incidence of these infections is increasing-largely because of rising numbers of immunocompromised patients, including those with neutropenia, human immunodeficiency virus, chronic immunosuppression, indwelling prostheses, burns, and diabetes mellitus, and those taking broad-spectrum antibiotics. Invasive fungal pathogens include primary mycotic organisms such as Histoplasma capsulatum, Coccidioides immitis, Blastomyces dermatitidis, and Paracoccidioides brasiliensis, which are true pathogens and inherently virulent...
July 2017: Radiographics: a Review Publication of the Radiological Society of North America, Inc
https://www.readbyqxmd.com/read/28560131/fatal-invasive-aspergillosis-caused-by-aspergillus-niger-after-bilateral-lung-transplantation
#13
Enora Atchade, Sylvain Jean-Baptiste, Sandrine Houzé, Claire Chabut, Laurent Massias, Yves Castier, Olivier Brugière, Hervé Mal, Philippe Montravers
Aspergillus niger is usually considered to be a low virulence fungus, not commonly reported to cause invasive infections. Invasive pulmonary aspergillosis due to Aspergillus niger was diagnosed in a 43-year-old woman following bilateral lung transplantation. Intravenous voriconazole failed to control progression of the disease. Despite salvage therapy with a combination of voriconazole and caspofungin for 23 days, the patient developed massive hemoptysis leading to death. The authors report the clinical features and treatment of this case...
September 2017: Medical Mycology Case Reports
https://www.readbyqxmd.com/read/28525266/gliotoxin-biosynthesis-structure-mechanism-and-metal-promiscuity-of-carboxypeptidase-glij
#14
Antoine Marion, Michael Groll, Daniel H Scharf, Kirstin Scherlach, Manuel Glaser, Holger Sievers, Michael Schuster, Christian Hertweck, Axel A Brakhage, Iris Antes, Eva M Huber
The formation of glutathione (GSH) conjugates, best known from the detoxification of xenobiotics, is a widespread strategy to incorporate sulfur into biomolecules. The biosynthesis of gliotoxin, a virulence factor of the human pathogenic fungus Aspergillus fumigatus, involves attachment of two GSH molecules and their sequential decomposition to yield two reactive thiol groups. The degradation of the GSH moieties requires the activity of the Cys-Gly carboxypeptidase GliJ, for which we describe the X-ray structure here...
June 6, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28515264/functional-characterization-of-the-copper-transcription-factor-mrpa%C3%A2-from-aspergillus-fumigatus
#15
Yong-Sung Park, Tae-Hyoung Kim, Cheol-Won Yun
Although copper functions as a cofactor in many physiological processes, copper overload leads to harmful effects in living cells. Thus, copper homeostasis is tightly regulated. However, detailed copper metabolic pathways have not yet been identified in filamentous fungi. In this report, we investigated the copper transcription factor AfMac1 (Aspergillus fumigatus Mac1 homologue), and identified its regulatory mechanism in A. fumigatus AfMac1 has domains homologous to the DNA- and copper-binding domains of Mac1 from Saccharomyces cerevisiae , and AfMac1 efficiently complemented Mac1 in S...
May 17, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/28489963/the-aspergillus-fumigatus-farnesyltransferase-%C3%AE-subunit-rama-mediates-growth-virulence-and-antifungal-susceptibility
#16
Tiffany S Norton, Qusai Al Abdallah, Amy M Hill, Rachel V Lovingood, Jarrod R Fortwendel
Post-translational prenylation mechanisms, including farnesylation and geranylgeranylation, mediate both subcellular localization and protein-protein interaction in eukaryotes. The prenyltransferase complex is an αβ heterodimer in which the essential α-subunit is common to both the farnesyltransferase and the geranylgeranyltransferase type-I enzymes. The β-subunit is unique to each enzyme. Farnesyltransferase activity is an important mediator of protein localization and subsequent signaling for multiple proteins, including Ras GTPases...
May 10, 2017: Virulence
https://www.readbyqxmd.com/read/28467895/aspergillus-fumigatus-copper-export-machinery-and-reactive-oxygen-intermediate-defense-counter-host-copper-mediated-oxidative-antimicrobial-offense
#17
Philipp Wiemann, Adi Perevitsky, Fang Yun Lim, Yana Shadkchan, Benjamin P Knox, Julio A Landero Figueora, Tsokyi Choera, Mengyao Niu, Andrew J Steinberger, Marcel Wüthrich, Rachel A Idol, Bruce S Klein, Mary C Dinauer, Anna Huttenlocher, Nir Osherov, Nancy P Keller
The Fenton-chemistry-generating properties of copper ions are considered a potent phagolysosome defense against pathogenic microbes, yet our understanding of underlying host/microbe dynamics remains unclear. We address this issue in invasive aspergillosis and demonstrate that host and fungal responses inextricably connect copper and reactive oxygen intermediate (ROI) mechanisms. Loss of the copper-binding transcription factor AceA yields an Aspergillus fumigatus strain displaying increased sensitivity to copper and ROI in vitro, increased intracellular copper concentrations, decreased survival in challenge with murine alveolar macrophages (AMΦs), and reduced virulence in a non-neutropenic murine model...
May 2, 2017: Cell Reports
https://www.readbyqxmd.com/read/28453536/rtfa-controls-development-secondary-metabolism-and-virulence-in-aspergillus-fumigatus
#18
Ryan R Myers, Timothy D Smith, Sherine F Elsawa, Olivier Puel, Souraia Tadrist, Ana M Calvo
Invasive aspergillosis by Aspergillus fumigatus is a leading cause of infection-related mortality in immune-compromised patients. In order to discover potential genetic targets to control A. fumigatus infections we characterized rtfA, a gene encoding a putative RNA polymerase II transcription elongation factor-like protein. Our recent work has shown that the rtfA ortholog in the model fungus Aspergillus nidulans regulates morphogenesis and secondary metabolism. The present study on the opportunistic pathogen A...
2017: PloS One
https://www.readbyqxmd.com/read/28447887/cyclopiazonic-acid-is-a-pathogenicity-factor-for-aspergillus-flavus-and-a-promising-target-for-screening-germplasm-for-ear-rot-resistance
#19
Subbaiah C Chalivendra, Catherine DeRobertis, Perng-Kuang Chang, Kenneth E Damann
Aspergillus flavus, an opportunistic pathogen, contaminates maize and other key crops with carcinogenic aflatoxins (AFs). Besides AFs, A. flavus makes many more secondary metabolites (SMs) whose toxicity in insects or vertebrates has been studied. However, the role of SMs in the invasion of plant hosts by A. flavus remains to be investigated. Cyclopiazonic acid (CPA), a neurotoxic SM made by A. flavus, is a nanomolar inhibitor of endoplasmic reticulum calcium ATPases (ECAs) and a potent inducer of cell death in plants...
May 2017: Molecular Plant-microbe Interactions: MPMI
https://www.readbyqxmd.com/read/28442603/aspergillus-fumigatus-trehalose-regulatory-subunit-homolog-moonlights-to-mediate-cell-wall-homeostasis-through-modulation-of-chitin-synthase-activity
#20
Arsa Thammahong, Alayna K Caffrey-Card, Sourabh Dhingra, Joshua J Obar, Robert A Cramer
Trehalose biosynthesis is found in fungi but not humans. Proteins involved in trehalose biosynthesis are essential for fungal pathogen virulence in humans and plants through multiple mechanisms. Loss of canonical trehalose biosynthesis genes in the human pathogen Aspergillus fumigatus significantly alters cell wall structure and integrity, though the mechanistic link between these virulence-associated pathways remains enigmatic. Here we characterize genes, called tslA and tslB, which encode proteins that contain domains similar to those corresponding to trehalose-6-phosphate phosphatase but lack critical catalytic residues for phosphatase activity...
April 25, 2017: MBio
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