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Pore forming toxins

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https://www.readbyqxmd.com/read/28106142/identification-of-lukpq-a-novel-equid-adapted-leukocidin-of-staphylococcus-aureus
#1
Gerrit Koop, Manouk Vrieling, Daniel M L Storisteanu, Laurence S C Lok, Tom Monie, Glenn van Wigcheren, Claire Raisen, Xiaoliang Ba, Nicholas Gleadall, Nazreen Hadjirin, Arjen J Timmerman, Jaap A Wagenaar, Heleen M Klunder, J Ross Fitzgerald, Ruth Zadoks, Gavin K Paterson, Carmen Torres, Andrew S Waller, Anette Loeffler, Igor Loncaric, Armando E Hoet, Karin Bergström, Luisa De Martino, Constança Pomba, Hermínia de Lencastre, Karim Ben Slama, Haythem Gharsa, Emily J Richardson, Edwin R Chilvers, Carla de Haas, Kok van Kessel, Jos A G van Strijp, Ewan M Harrison, Mark A Holmes
Bicomponent pore-forming leukocidins are a family of potent toxins secreted by Staphylococcus aureus, which target white blood cells preferentially and consist of an S- and an F-component. The S-component recognizes a receptor on the host cell, enabling high-affinity binding to the cell surface, after which the toxins form a pore that penetrates the cell lipid bilayer. Until now, six different leukocidins have been described, some of which are host and cell specific. Here, we identify and characterise a novel S...
January 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28088448/fast-formation-of-low-defect-density-tethered-bilayers-by-fusion-of-multilamellar-vesicles
#2
Tadas Ragaliauskas, Mindaugas Mickevicius, Bozena Rakovska, Tadas Penkauskas, David J Vanderah, Frank Heinrich, Gintaras Valincius
A facile and reproducible preparation of surface-supported lipid bilayers is essential for fundamental membrane research and biotechnological applications. We demonstrate that multilamellar vesicles fuse to molecular-anchor-grafted surfaces yielding low-defect-density, tethered bilayer membranes. Continuous bilayers are formed within 10min, while the electrically insulating bilayers with <0.1μm(-2) defect density can be accomplished within 60min. Surface plasmon resonance spectroscopy indicates that an amount of lipid material transferred from vesicles to a surface is inversely proportional to the density of an anchor, while the total amount of lipid that includes tethered and transferred lipid remains constant within 5% standard error...
January 11, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28081446/host-to-host-transmission-of-streptococcus-pneumoniae-is-driven-by-its-inflammatory-toxin-pneumolysin
#3
M Ammar Zafar, Yang Wang, Shigeto Hamaguchi, Jeffrey N Weiser
Host-to-host transmission is a critical step for infection. Here we studied transmission of the opportunistic pathogen Streptococcus pneumoniae in an infant mouse model. Transmission from nasally colonized pups required high levels of bacterial shedding in nasal secretions and was temporally correlated with, and dependent upon, the acute inflammatory response. Pneumolysin, a pore-forming cytotoxin and major virulence determinant, was both necessary and sufficient to promote inflammation, which increased shedding and allowed for intralitter transmission...
January 11, 2017: Cell Host & Microbe
https://www.readbyqxmd.com/read/28074026/promyelocytic-leukemia-protein-pml-controls-listeria-monocytogenes-infection
#4
David Ribet, Valérie Lallemand-Breitenbach, Omar Ferhi, Marie-Anne Nahori, Hugo Varet, Hugues de Thé, Pascale Cossart
: The promyelocytic leukemia protein (PML) is the main organizer of stress-responsive subnuclear structures called PML nuclear bodies. These structures recruit multiple interactors and modulate their abundance or their posttranslational modifications, notably by the SUMO ubiquitin-like modifiers. The involvement of PML in antiviral responses is well established. In contrast, the role of PML in bacterial infection remains poorly characterized. Here, we show that PML restricts infection by the pathogenic bacterium Listeria monocytogenes but not by Salmonella enterica serovar Typhimurium...
January 10, 2017: MBio
https://www.readbyqxmd.com/read/28062388/netf-producing-clostridium-perfringens-clonality-and-plasmid-pathogenicity-loci-analysis
#5
Iman Mehdizadeh Gohari, Andrew M Kropinski, Scott J Weese, Ashley E Whitehead, Valeria R Parreira, Patrick Boerlin, John F Prescott
Clostridium perfringens is an important cause of foal necrotizing enteritis and canine acute hemorrhagic diarrhea. A major virulence determinant of the strains associated with these diseases appears to be a beta-sheet pore-forming toxin, NetF, encoded within a pathogenicity locus (NetF locus) on a large tcp-conjugative plasmid. Strains producing NetF also produce the putative toxin NetE, encoded within the same pathogenicity locus, as well as CPE enterotoxin and CPB2 on a second plasmid, and sometimes the putative toxin NetG within a pathogenicity locus (NetG locus) on another separate large conjugative plasmid...
January 3, 2017: Infection, Genetics and Evolution
https://www.readbyqxmd.com/read/28060924/the-effector-domain-region-of-the-vibrio-vulnificus-martx-toxin-confers-biphasic-epithelial-barrier-disruption-and-is-essential-for-systemic-spread-from-the-intestine
#6
Hannah E Gavin, Nike T Beubier, Karla J F Satchell
Vibrio vulnificus causes highly lethal bacterial infections in which the Multifunctional Autoprocessing Repeats-in-Toxins (MARTX) toxin product of the rtxA1 gene is a key virulence factor. MARTX toxins are secreted proteins up to 5208 amino acids in size. Conserved MARTX N- and C-terminal repeat regions work in concert to form pores in eukaryotic cell membranes, through which the toxin's central region of modular effector domains is translocated. Upon inositol hexakisphosphate-induced activation of the of the MARTX cysteine protease domain (CPD) in the eukaryotic cytosol, effector domains are released from the holotoxin by autoproteolytic activity...
January 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28048967/the-pore-forming-capacity-of-sticholysin-i-in-dipalmitoyl-phosphatidyl-vesicles-is-tuned-by-osmotic-stress
#7
M Ahumada, C Calderon, E Lissi, C Alvarez, M E Lanio
The osmotic condition modulates the properties of liposomes, particularly those related to their stability and response to external agents such as membrane-active proteins or peptides. In a previous work, we have demonstrated that an osmotic shock can increase, per se, water influx/efflux and the exit of the fluorophore calcein entrapped in the aqueous pool of dipalmitoylphosphatidylcholine (DPPC) and DPPC:sphingomyelin (SM) large unilamellar vesicles (LUVs), suggesting a loss of integrity of the liposome bilayer...
December 31, 2016: Chemistry and Physics of Lipids
https://www.readbyqxmd.com/read/28039206/endoplasmic-reticulum-chaperone-gp96-controls-actomyosin-dynamics-and-protects-against-pore-forming-toxins
#8
Francisco Sarmento Mesquita, Cláudia Brito, Maria J Mazon Moya, Jorge Campos Pinheiro, Serge Mostowy, Didier Cabanes, Sandra Sousa
During infection, plasma membrane (PM) blebs protect host cells against bacterial pore-forming toxins (PFTs), but were also proposed to promote pathogen dissemination. However, the details and impact of blebbing regulation during infection remained unclear. Here, we identify the endoplasmic reticulum chaperone Gp96 as a novel regulator of PFT-induced blebbing. Gp96 interacts with non-muscle myosin heavy chain IIA (NMHCIIA) and controls its activity and remodelling, which is required for appropriate coordination of bleb formation and retraction...
December 30, 2016: EMBO Reports
https://www.readbyqxmd.com/read/28003061/azadinium-poporum-from-the-argentine-continental-shelf-southwestern-atlantic-produces-azaspiracid-2-and-azaspiracid-2-phosphate
#9
Urban Tillmann, C Marcela Borel, Facundo Barrera, Rubén Lara, Bernd Krock, Gastón O Almandoz, Matthias Witt, Nicole Trefault
The marine dinophycean genus Azadinium has been identified as the primary source of azaspiracids (AZA), a group of lipophilic phycotoxins known to accumulate in shellfish. Blooms of Azadinium in the southern Atlantic off Argentina have been described from the 1990s, but due to a lack of cultures, the diversity of South-Atlantic Azadinium has not yet been fully explored and their toxin production potential is completely unknown. During a spring 2010 research cruise covering the El Rincón (ER) estuarine system (North Patagonian coast, Argentina, Southwestern Atlantic) a search was conducted for the presence of Azadinium...
January 2016: Harmful Algae
https://www.readbyqxmd.com/read/27995777/a-return-to-the-pore-dissecting-bacillus-thuringiensis-toxin-mode-of-action-via-voltage-clamp-experiments
#10
David G Heckel
Pore-forming toxins from Bacillus thuringiensis are increasingly used in crop protection, but evolution of resistance in crop pests threatens their continued deployment. A study by Tanaka et al. shows how voltage clamp experiments that quantify pore formation can be used to dissect toxin mode of action, thereby revealing unexpected complexities that could be exploited to counter resistance.
December 2016: FEBS Journal
https://www.readbyqxmd.com/read/27993565/acylation-of-the-bordetella-pertussis-cyaa-hemolysin-functional-implications-for-efficient-membrane-insertion-and-pore-formation
#11
Kanungsuk Meetum, Chompounoot Imtong, Gerd Katzenmeier, Chanan Angsuthanasombat
Previously, the ~130-kDa CyaA-hemolysin domain (CyaA-Hly) from Bordetella pertussis co-expressed with CyaC-acyltransferase in Escherichia coli was demonstrated to be palmitoylated at Lys(983) and thus activated its hemolytic activity against target erythrocytes. Here, we report the functional importance of Lys(983)-palmitoylation for membrane insertion and pore formation of CyaA-Hly. Intrinsic fluorescence emissions of both non-acylated CyaA-Hly (NA/CyaA-Hly) and CyaA-Hly were indistinguishable, suggesting no severe conformational change upon acylation at Lys(983)...
December 18, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27978428/pore-forming-toxins-trigger-the-purge
#12
Alessandro Bonfini, Nicolas Buchon
The intestinal epithelium responds to pathogens by coordinating microbial elimination with tissue repair, both required to survive an infection. In this issue of Cell Host & Microbe, Lee et al. (2016) discover a rapid and evolutionarily conserved response to pore-forming toxins in the gut, involving cytoplasm ejection and enterocyte regrowth.
December 14, 2016: Cell Host & Microbe
https://www.readbyqxmd.com/read/27974664/aggregatibacter-actinomycetemcomitans-induced-hypercitrullination-links-periodontal-infection-to-autoimmunity-in-rheumatoid-arthritis
#13
Maximilian F Konig, Loreto Abusleme, Jesper Reinholdt, Robert J Palmer, Ricardo P Teles, Kevon Sampson, Antony Rosen, Peter A Nigrovic, Jeremy Sokolove, Jon T Giles, Niki M Moutsopoulos, Felipe Andrade
A bacterial etiology of rheumatoid arthritis (RA) has been suspected since the beginnings of modern germ theory. Recent studies implicate mucosal surfaces as sites of disease initiation. The common occurrence of periodontal dysbiosis in RA suggests that oral pathogens may trigger the production of disease-specific autoantibodies and arthritis in susceptible individuals. We used mass spectrometry to define the microbial composition and antigenic repertoire of gingival crevicular fluid in patients with periodontal disease and healthy controls...
December 14, 2016: Science Translational Medicine
https://www.readbyqxmd.com/read/27965453/staphylococcus-aureus-leukocidin-luked-and-hiv-1-gp120-target-different-sequence-determinants-on-ccr5
#14
Kayan Tam, Megan Schultz, Tamara Reyes-Robles, Bénédicte Vanwalscappel, Joshua Horton, Francis Alonzo, Beili Wu, Nathaniel R Landau, Victor J Torres
: Leukocidin ED (LukED) is a bicomponent pore-forming toxin produced by Staphylococcus aureus that lyses host cells by targeting the chemokine receptors CC chemokine receptor type 5 (CCR5), CXCR1, CXCR2, and DARC. In addition to its role as a receptor for LukED, CCR5 is the major coreceptor for primary isolates of human immunodeficiency virus type 1 (HIV-1) and has been extensively studied. To compare how LukED and HIV-1 target CCR5, we analyzed their respective abilities to use CCR5/CCR2b chimeras to mediate cytotoxicity and virus entry...
December 13, 2016: MBio
https://www.readbyqxmd.com/read/27965452/bystander-host-cell-killing-effects-of-clostridium-perfringens-enterotoxin
#15
Archana Shrestha, Matthew R Hendricks, Jennifer M Bomberger, Bruce A McClane
: Clostridium perfringens enterotoxin (CPE) binds to claudin receptors, e.g., claudin-4, and then forms a pore that triggers cell death. Pure cultures of host cells that do not express claudin receptors, e.g., fibroblasts, are unaffected by pathophysiologically relevant CPE concentrations in vitro However, both CPE-insensitive and CPE-sensitive host cells are present in vivo Therefore, this study tested whether CPE treatment might affect fibroblasts when cocultured with CPE-sensitive claudin-4 fibroblast transfectants or Caco-2 cells...
December 13, 2016: MBio
https://www.readbyqxmd.com/read/27964891/formation-of-hybrid-bilayers-on-silanized-thin-film-ti-electrode
#16
A Valiūnienė, T Petrulionienė, I Balevičiūtė, L Mikoliūnaitė, G Valinčius
Phospholipid bilayer membranes are essential elements of living organisms as they form boundaries between the intracellular cytoplasm and the extracellular environment, as well as organelles. In this work we report on our attempts to assemble artificial phospholipid bilayer model membranes on Ti surface. To provide hydrophobic cushion for phospholipids, the surface of a thin-film Ti electrode was initially functionalized with trichloro(octadecyl)silane (OTS). Increased hydrophobicity of the solid support allowed vesicle fusion and the formation of a hybrid 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) bilayer, as probed by the electrochemical impedance spectroscopy (EIS), contact angle measurements (CA) also by the Fourier transform-infrared (FT-IR) spectroscopy, spectroscopic ellipsometry (SE) and atomic force microscopy (AFM)...
December 10, 2016: Chemistry and Physics of Lipids
https://www.readbyqxmd.com/read/27941639/evolution-of-the-cytolytic-pore-forming-proteins-actinoporins-in-sea-anemones
#17
Jason Macrander, Marymegan Daly
Sea anemones (Cnidaria, Anthozoa, and Actiniaria) use toxic peptides to incapacitate and immobilize prey and to deter potential predators. Their toxin arsenal is complex, targeting a variety of functionally important protein complexes and macromolecules involved in cellular homeostasis. Among these, actinoporins are one of the better characterized toxins; these venom proteins form a pore in cellular membranes containing sphingomyelin. We used a combined bioinformatic and phylogenetic approach to investigate how actinoporins have evolved across three superfamilies of sea anemones (Actinioidea, Metridioidea, and Actinostoloidea)...
December 8, 2016: Toxins
https://www.readbyqxmd.com/read/27934826/molecular-characterisation-of-panton-valentine-leucocidin-producing-methicillin-resistant-staphylococcus-aureus-clones-isolated-from-the-main-hospitals-in-taif-ksa
#18
E M Eed, M M Ghonaim, Y M Hussein, S S Al-Shehri, A S Khalifa
INTRODUCTION: Panton-Valentine leucocidin (PVL) is a bicomponent pore-forming cytolytic toxin encoded by the lukF-PV and lukS-PV genes. Community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) may carry the pvl genes which may be related to increased disease severity. This study aimed to characterise the PVL-producing MRSA recovered from different Taif Hospitals, Saudi Arabia. METHODS: The study included 45 hospital-acquired-MRSA (HA-MRSA) and 26 CA-MRSA strains which were identified from 445 S...
October 2016: Indian Journal of Medical Microbiology
https://www.readbyqxmd.com/read/27933793/differential-effect-of-membrane-composition-on-the-pore-forming-ability-of-four-different-sea-anemone-actinoporins
#19
Sara García-Linares, Esperanza Rivera-de-Torre, Koldo Morante, Kouhei Tsumoto, Jose M M Caaveiro, José G Gavilanes, J Peter Slotte, Álvaro Martínez-Del-Pozo
Sea anemone actinoporins constitute a protein family of multigene pore-forming toxins (PFT). Equinatoxin II (EqtII), fragaceatoxin C (FraC), and sticholysins I and II (StnI and StnII, respectively), produced by three different sea anemone species, are the only actinoporins whose molecular structures have been studied in depth. These four proteins show high sequence identities and practically coincident three-dimensional structures. However, their pore-forming activity can be quite different depending on the model lipid system employed, a feature that has not been systematically studied before...
December 6, 2016: Biochemistry
https://www.readbyqxmd.com/read/27933775/role-of-the-tryptophan-residues-in-the-specific-interaction-of-the-sea-anemone-stichodactyla-helianthus-s-actinoporin-sticholysin-ii-with-biological-membranes
#20
Sara García-Linares, Terhi Maula, Esperanza Rivera-de-Torre, José G Gavilanes, J Peter Slotte, Álvaro Martínez-Del-Pozo
Actinoporins are pore-forming toxins from sea anemones. Upon interaction with sphingomyelin-containing bilayers, they become integral oligomeric membrane structures that form a pore. Sticholysin II from Stichodactyla helianthus contains five tryptophans located at strategic positions; its role has now been studied using different mutants. Results show that W43 and W115 play a determinant role in maintaining the high thermostability of the protein, while W146 provides specific interactions for protomer-protomer assembly...
November 22, 2016: Biochemistry
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