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'Aspergillus' and 'virulence'

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https://www.readbyqxmd.com/read/28525266/gliotoxin-biosynthesis-structure-mechanism-and-metal-promiscuity-of-carboxypeptidase-glij
#1
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...
May 19, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28515264/functional-characterization-of-the-copper-transcription-factor-mrpa%C3%A2-from-aspergillus-fumigatus
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
https://www.readbyqxmd.com/read/28393907/involvement-of-a-velvet-protein-clvelb-in-the-regulation-of-vegetative-differentiation-oxidative-stress-response-secondary-metabolism-and-virulence-in-curvularia-lunata
#8
Jin-Xin Gao, Chuan-Jin Yu, Meng Wang, Jia-Nan Sun, Ya-Qian Li, Jie Chen
The ortholog of Aspergillus nidulans VelB, which is known as ClVelB, was studied to gain a broader insight into the functions of a velvet protein in Curvularia lunata. With the expected common and specific functions of ClVelB, the deletion of clvelB results in similar though not identical phenotypes. The pathogenicity assays revealed that ΔClVelB was impaired in colonizing the host tissue, which corresponds to the finding that ClVelB controls the production of conidia and the methyl 5-(hydroxymethyl) furan-2-carboxylate toxin in C...
April 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28381925/molecular-insights-into-pathogenesis-and-infection-with-aspergillus-fumigatus
#9
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/28367141/functional-investigation-of-iron-responsive-microsomal-proteins-including-mirc-in-aspergillus-fumigatus
#10
Eoin D Mulvihill, Nicola M Moloney, Rebecca A Owens, Stephen K Dolan, Lauren Russell, Sean Doyle
The functionality of many microsome-associated proteins which exhibit altered abundance in response to iron limitation in Aspergillus fumigatus is unknown. Here, we generate and characterize eight gene deletion strains, and of most significance reveal that MirC (AFUA_2G05730) contributes to the maintenance of intracellular siderophore [ferricrocin (FC)] levels, augments conidiation, confers protection against oxidative stress, exhibits an intracellular localization and contributes to fungal virulence in the Galleria mellonella animal model system...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28346365/an-amylase-like-protein-amyd-is-the-major-negative-regulator-for-%C3%AE-glucan-synthesis-in-aspergillus-nidulans-during-the-asexual-life-cycle
#11
Xiaoxiao He, Shengnan Li, Susan Kaminskyj
α-Glucan affects fungal cell-cell interactions and is important for the virulence of pathogenic fungi. Interfering with production of α-glucan could help to prevent fungal infection. In our previous study, we reported that an amylase-like protein, AmyD, could repress α-glucan accumulation in Aspergillus nidulans. However, the underlying molecular mechanism was not clear. Here, we examined the localization of AmyD and found it was a membrane-associated protein. We studied AmyD function in α-glucan degradation, as well as with other predicted amylase-like proteins and three annotated α-glucanases...
March 27, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28301237/aspergillosis-a-natural-infection-in-poultry-mycological-and-molecular-characterization-and-determination-of-gliotoxin-in-aspergillus-fumigatus-isolates
#12
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/28298477/central-role-of-the-trehalose-biosynthesis-pathway-in-the-pathogenesis-of-human-fungal-infections-opportunities-and-challenges-for-therapeutic-development
#13
REVIEW
Arsa Thammahong, Srisombat Puttikamonkul, John R Perfect, Richard G Brennan, Robert A Cramer
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 in a wide variety of organisms, including human-pathogenic fungi, but not in humans...
June 2017: Microbiology and Molecular Biology Reviews: MMBR
https://www.readbyqxmd.com/read/28265787/isolation-and-characterisation-of-an-enterocin-p-producing-enterococcus-lactis-strain-from-a-fresh-shrimp-penaeus-vannamei
#14
Olfa Ben Braïek, Hamdi Ghomrassi, Paola Cremonesi, Stefano Morandi, Yannick Fleury, Patrick Le Chevalier, Khaled Hani, Omrane Bel Hadj, Taoufik Ghrairi
Screening for lactic acid bacteria (LAB) from fresh shrimp samples (Penaeus vannamei) collected from retail seafood markets in the Tunisian's coast, resulted in the isolation of an Enterococcus strain termed Q1. This strain was selected for its antagonistic activity against pathogenic bacteria such as Listeria monocytogenes, Pseudomonas aeruginosa, Lactococcus garvieae and against fungi (Aspergillus niger and Fusarium equiseti). The Q1 strain was characterised using standard morphological and biochemical tests, growth assays at different temperatures, pH and salinity...
March 7, 2017: Antonie Van Leeuwenhoek
https://www.readbyqxmd.com/read/28261252/rna-interference-rnai-as-a-potential-tool-for-control-of-mycotoxin-contamination-in-crop-plants-concepts-and-considerations
#15
REVIEW
Rajtilak Majumdar, Kanniah Rajasekaran, Jeffrey W Cary
Mycotoxin contamination in food and feed crops is a major concern worldwide. Fungal pathogens of the genera Aspergillus. Fusarium, and Penicillium are a major threat to food and feed crops due to production of mycotoxins such as aflatoxins, 4-deoxynivalenol, patulin, and numerous other toxic secondary metabolites that substantially reduce the value of the crop. While host resistance genes are frequently used to introgress disease resistance into elite germplasm, either through traditional breeding or transgenic approaches, such resistance is often compromised by the evolving pathogen over time...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/28257463/polygalacturonase-gene-pgxb-in-aspergillus-niger-is-a-virulence-factor-in-apple-fruit
#16
Cheng-Qian Liu, Kang-Di Hu, Ting-Ting Li, Ying Yang, Feng Yang, Yan-Hong Li, He-Ping Liu, Xiao-Yan Chen, Hua Zhang
Aspergillus niger, a saprophytic fungus, is widely distributed in soil, air and cereals, and can cause postharvest diseases in fruit. Polygalacturonase (PG) is one of the main enzymes in fungal pathogens to degrade plant cell wall. To evaluate whether the deletion of an exo-polygalacturonase gene pgxB would influence fungal pathogenicity to fruit, pgxB gene was deleted in Aspergillus niger MA 70.15 (wild type) via homologous recombination. The ΔpgxB mutant showed similar growth behavior compared with the wild type...
2017: PloS One
https://www.readbyqxmd.com/read/28251756/functional-genomics-guided-discovery-of-a-light-activated-phytotoxin-in-the-wheat-pathogen-parastagonospora-nodorum-via-pathway-activation
#17
Yit-Heng Chooi, Guozhi Zhang, Jinyu Hu, Mariano Jordi Muria-Gonzalez, Phuong N Tran, Amber Pettitt, Alexander G Maier, Russell A Barrow, Peter S Solomon
Parastagonospora nodorum is an important pathogen of wheat. The contribution of secondary metabolites to this pathosystem is poorly understood. A biosynthetic gene cluster (SNOG_08608-08616) has been shown to be upregulated during the late stage of P. nodorum wheat leaf infection. The gene cluster shares several homologues with the Cercospora nicotianae CTB gene cluster encoding the biosynthesis of cercosporin. Activation of the gene cluster by overexpression (OE) of the transcription factor gene (SNOG_08609) in P...
March 2, 2017: Environmental Microbiology
https://www.readbyqxmd.com/read/28223452/heterogeneity-confounds-establishment-of-a-model-microbial-strain
#18
Nancy P Keller
Aspergillus fumigatus is a ubiquitous environmental mold and the leading cause of diverse human diseases ranging from allergenic bronchopulmonary aspergillosis (ABPA) to invasive pulmonary aspergillosis (IPA). Experimental investigations of the biology and virulence of this opportunistic pathogen have historically used a few type strains; however, it is increasingly observed with this fungus that heterogeneity among isolates potentially confounds the use of these reference isolates. Illustrating this point, Kowalski et al...
February 21, 2017: MBio
https://www.readbyqxmd.com/read/28217776/iron-acquisition-in-fungal-pathogens-of-humans
#19
Gaurav Bairwa, Won Hee Jung, James W Kronstad
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 heme and hemoglobin in the virulence of pathogenic yeasts...
February 20, 2017: Metallomics: Integrated Biometal Science
https://www.readbyqxmd.com/read/28174315/a-novel-phosphoregulatory-switch-controls-the-activity-and-function-of-the-major-catalytic-subunit-of-protein-kinase-a-in-aspergillus-fumigatus
#20
E Keats Shwab, Praveen R Juvvadi, Greg Waitt, Erik J Soderblom, M Arthur Moseley, Nathan I Nicely, Yohannes G Asfaw, William J Steinbach
Invasive aspergillosis (IA), caused by the filamentous fungal pathogen Aspergillus fumigatus, is a major cause of death among immunocompromised patients. The cyclic AMP/protein kinase A (PKA) signaling pathway is essential for hyphal growth and virulence of A. fumigatus, but the mechanism of regulation of PKA remains largely unknown. Here, we discovered a novel mechanism for the regulation of PKA activity in A. fumigatus via phosphorylation of key residues within the major catalytic subunit, PkaC1. Phosphopeptide enrichment and tandem mass spectrometry revealed the phosphorylation of PkaC1 at four sites (S175, T331, T333, and T337) with implications for important and diverse roles in the regulation of A...
February 7, 2017: MBio
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