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Pore forming toxins

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https://www.readbyqxmd.com/read/29768707/albumin-apheresis-for-artificial-liver-support-in-vitro-testing-of-a-novel-filter
#1
Tomasz Piatek, Joanna Giebultowicz, Marieke Rüth, Horst-Dieter Lemke, Florian Bonn, Piotr Wroczynski, Piotr Malkowski, Jacek Rozga
Currently there is no direct therapy for liver failure. We have previously described selective plasma exchange therapy using a hemofilter permeable to substances that have a molecular mass of up to 100 kDa. The proof-of-concept studies and a Phase I study in patients with decompensated cirrhosis demonstrated that hemofiltration using an albumin-leaking membrane is safe and effective in removing target molecules, alleviating severe encephalopathy and improving blood chemistry. In this study a novel large-pore filter for similar clinical application is described...
May 16, 2018: Therapeutic Apheresis and Dialysis
https://www.readbyqxmd.com/read/29758533/antimicrobial-resistance-biofilm-formation-and-virulence-reveal-actinobacillus-pleuropneumoniae-strains-pathogenicity-complexity
#2
Monalessa Fábia Pereira, Ciro César Rossi, Larissa Eler Seide, Sebastião Martins Filho, Cláudia de Melo Dolinski, Denise Mara Soares Bazzolli
Porcine pleuropneumonia is an important cause of lowered productivity and economic loss in the pig industry worldwide, associated primarily with Actinobacillus pleuropneumoniae infection. Its colonization and persistence within the upper respiratory tract of affected pigs depends upon interactions between a number of genetically controlled virulence factors, such as pore-forming repeats-in-toxin exoproteins, biofilm formation, and antimicrobial resistance. This study investigated correlations between biofilm-forming capacity, antimicrobial resistance, and virulence of A...
May 7, 2018: Research in Veterinary Science
https://www.readbyqxmd.com/read/29752379/rapid-remodeling-of-the-host-epithelial-cell-proteome-by-the-listeriolysin-o-pore-forming-toxin
#3
Julien Karim Malet, Francis Impens, Filipe Carvalho, Mélanie Anne Hamon, Pascale Cossart, David Ribet
Bacterial pathogens use various strategies to interfere with host cell functions. Among these strategies, bacteria modulate host gene transcription, thereby modifying the set of proteins synthetized by the infected cell. Bacteria can also target pre-existing host proteins and modulate their post-translational modifications or trigger their degradation. Analysis of protein levels variations in host cells during infection allows to integrate both transcriptional and post-transcriptional regulations induced by pathogens...
May 11, 2018: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/29728606/structure-and-mechanism-of-the-two-component-%C3%AE-helical-pore-forming-toxin-yaxab
#4
Bastian Bräuning, Eva Bertosin, Florian Praetorius, Christian Ihling, Alexandra Schatt, Agnes Adler, Klaus Richter, Andrea Sinz, Hendrik Dietz, Michael Groll
Pore-forming toxins (PFT) are virulence factors that transform from soluble to membrane-bound states. The Yersinia YaxAB system represents a family of binary α-PFTs with orthologues in human, insect, and plant pathogens, with unknown structures. YaxAB was shown to be cytotoxic and likely involved in pathogenesis, though the molecular basis for its two-component lytic mechanism remains elusive. Here, we present crystal structures of YaxA and YaxB, together with a cryo-electron microscopy map of the YaxAB complex...
May 4, 2018: Nature Communications
https://www.readbyqxmd.com/read/29722060/structure-and-properties-of-ab21-a-novel-a-bisporus-protein-with-structural-relation-to-bacterial-pore-forming-toxins
#5
Jan Komárek, Eva Ivanov Kavková, Josef Houser, Aneta Horáčková, Jitka Ždánská, Gabriel Demo, Michaela Wimmerová
We report the characterization of the dimeric protein AB21 from Agaricus bisporus, one of the most commonly and widely consumed mushrooms in the world. The protein shares no significant sequence similarity with any protein of known function, and it is the first characterized member of its protein family. The coding sequence of the ab21 gene was determined and the protein was expressed in E. coli in a recombinant form. We demonstrated a high thermal and pH stability of AB21 and proved the weak affinity of the protein to divalent ions of some transition metals (nickel, zinc, cadmium and cobalt)...
May 2, 2018: Proteins
https://www.readbyqxmd.com/read/29720597/-19-f-nmr-studies-provide-insights-into-lipid-membrane-interactions-of-listeriolysin-o-a-pore-forming-toxin-from-listeria-monocytogenes
#6
Mirijam Kozorog, Marc-Antoine Sani, Martina Lenarčič Živković, Gregor Ilc, Vesna Hodnik, Frances Separovic, Janez Plavec, Gregor Anderluh
Listeria monocytogenes is a mammalian pathogen that causes gastroenteritis, miscarriages and infections of the central nervous system in immunocompromised individuals. Its main virulence factor is listeriolysin O (LLO), a pore-forming cholesterol-dependent cytolysin (CDC), which enables bacterial escape from the phagolysosome and contributes to bacterial pathogenicity. Details of cholesterol (Chol) recognition and membrane binding mechanisms by LLO are still not known. Here we used 19 F-NMR spectroscopy in order to assess LLO-Chol interactions in solution and in a Chol-rich membrane environment...
May 2, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29687242/confocal-micrographs-automated-segmentation-and-quantitative-shape-analysis-of-neuronal-cells-treated-with-ostreolysin-a-pleurotolysin-b-pore-forming-complex
#7
Lazar Kopanja, Zorana Kovacevic, Marin Tadic, Monika Cecilija Žužek, Milka Vrecl, Robert Frangež
Detailed shape analysis of cells is important to better understand the physiological mechanisms of toxins and determine their effects on cell morphology. This study aimed to develop a procedure for accurate morphological analysis of cell shape and use it as a tool to estimate toxin activity. With the aim of optimizing the method of cell morphology analysis, we determined the influence of ostreolysin A and pleurotolysin B complex (OlyA/PlyB) on the morphology of murine neuronal NG108-15 cells. A computational method was introduced and successfully applied to quantify morphological attributes of the NG108-15 cell line before and after 30 and 60 min exposure to OlyA/PlyB using confocal microscopy...
April 23, 2018: Histochemistry and Cell Biology
https://www.readbyqxmd.com/read/29679741/pneumolysin-damaged-cells-benefit-from-non-homogenous-toxin-binding-to-cholesterol-rich-membrane-domains
#8
Patrick Drücker, Simon Bachler, Heidi Wolfmeier, Roman Schoenauer, René Köffel, Viktoria S Babiychuk, Petra S Dittrich, Annette Draeger, Eduard B Babiychuk
Nucleated cells eliminate lesions induced by bacterial pore-forming toxins, such as pneumolysin via shedding patches of damaged plasmalemma into the extracellular milieu. Recently, we have shown that the majority of shed pneumolysin is present in the form of inactive pre-pores. This finding is surprising considering that shedding is triggered by Ca2+ -influx following membrane perforation and therefore is expected to positively discriminate for active pores versus inactive pre-pores. Here we provide evidence for the existence of plasmalemmal domains that are able to attract pneumolysin at high local concentrations...
April 18, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29643440/bacterial-pore-forming-toxins-promote-the-activation-of-caspases-in-parallel-to-necroptosis-to-enhance-alarmin-release-and-inflammation-during-pneumonia
#9
Norberto Gonzalez-Juarbe, Kelley M Bradley, Ashleigh N Riegler, Luis F Reyes, Terry Brissac, Sang-Sang Park, Marcos I Restrepo, Carlos J Orihuela
Pore-forming toxins are the most common virulence factor in pathogenic bacteria. They lead to membrane permeabilization and cell death. Herein, we show that respiratory epithelial cells (REC) undergoing bacterial pore-forming toxin (PFT)-induced necroptosis simultaneously experienced caspase activation independently of RIPK3. MLKL deficient REC treated with a pan-caspase inhibitor were protected in an additive manner against PFT-induced death. Subsequently, cleaved versions of caspases-2, -4 and -10 were detected within REC undergoing necroptosis by immunoblots and monoclonal antibody staining...
April 11, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29625104/structural-requirement-of-the-hydrophobic-region-of-the-bordetella-pertussis-cyaa-hemolysin-for-functional-association-with-cyac-acyltransferase-in-toxin-acylation
#10
Veerada Raksanoh, Panchika Prangkio, Chompounoot Imtong, Niramon Thamwiriyasati, Kittipong Suvarnapunya, Lalida Shank, Chanan Angsuthanasombat
Previously, we demonstrated that the ∼130-kDa CyaA-hemolysin (CyaA-Hly, Met482 -Arg1706 ) from Bordetella pertussis was palmitoylated at Lys983 when co-expressed with CyaC-acyltransferase in Escherichia coli, and thus activated its hemolytic activity. Here, further investigation on a possible requirement of the N-terminal hydrophobic region (HP, Met482 -Leu750 ) for toxin acylation was performed. The ∼100-kDa RTX (Repeat-in-ToXin) fragment (CyaA-RTX, Ala751 -Arg1706 ) containing the K983 -acylation region (AR, Ala751 -Gln1000 ), but lacking HP, was co-produced with CyaC in E...
April 3, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29621942/intestinal-lesions-in-dogs-with-acute-hemorrhagic-diarrhea-syndrome-associated-with-netf-positive-clostridium-perfringens-type-a
#11
Miriam Leipig-Rudolph, Kathrin Busch, John F Prescott, Iman Mehdizadeh Gohari, Christian M Leutenegger, Walter Hermanns, Georg Wolf, Katrin Hartmann, Jutta Verspohl, Stefan Unterer
Acute hemorrhagic diarrhea syndrome (AHDS), formerly named canine hemorrhagic gastroenteritis, is one of the most common causes of acute hemorrhagic diarrhea in dogs, and is characterized by acute onset of diarrhea, vomiting, and hemoconcentration. To date, histologic examinations have been limited to postmortem specimens of only a few dogs with AHDS. Thus, the aim of our study was to describe in detail the distribution, character, and grade of microscopic lesions, and to investigate the etiology of AHDS. Our study comprised 10 dogs with AHDS and 9 control dogs of various breeds, age, and sex...
April 1, 2018: Journal of Veterinary Diagnostic Investigation
https://www.readbyqxmd.com/read/29575515/conserved-structural-features-anchor-biofilm-associated-rtx-adhesins-to-the-outer-membrane-of-bacteria
#12
Shuaiqi Guo, David N Langelaan, Sean W Phippen, Steven P Smith, Ilja K Voets, Peter L Davies
Repeats-In-Toxin (RTX) adhesins are present in many Gram-negative bacteria to facilitate biofilm formation. Previously, we reported that the 1.5-MDa RTX adhesin (MpIBP) from the Antarctic bacterium, Marinomonas primoryensis, is tethered to the bacterial cell surface via its N-terminal Region I (RI). Here, we show the detailed structural features of RI. It has an N-terminal periplasmic retention domain (RIN), a central domain (RIM) that can insert into the β-barrel of an outer-membrane pore protein during MpIBP secretion, and three extracellular domains at its C terminus (RIC) that transition the protein into the extender region (RII)...
March 25, 2018: FEBS Journal
https://www.readbyqxmd.com/read/29563565/engineering-bacillus-thuringiensis-cyt1aa-toxin-specificity-from-dipteran-to-lepidopteran-toxicity
#13
Mary-Carmen Torres-Quintero, Isabel Gómez, Sabino Pacheco, Jorge Sánchez, Humberto Flores, Joel Osuna, Gretel Mendoza, Mario Soberón, Alejandra Bravo
The Cyt and Cry toxins are different pore-forming proteins produced by Bacillus thuringiensis bacteria, and used in insect-pests control. Cry-toxins have a complex mechanism involving interaction with several proteins in the insect gut such as aminopeptidase N (APN), alkaline phosphatase (ALP) and cadherin (CAD). It was shown that the loop regions of domain II of Cry toxins participate in receptor binding. Cyt-toxins are dipteran specific and interact with membrane lipids. We show that Cry1Ab domain II loop3 is involved in binding to APN, ALP and CAD receptors since point mutation Cry1Ab-G439D affected binding to these proteins...
March 21, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29559575/hitting-with-a-bam-selective-killing-by-lectin-like-bacteriocins
#14
Maarten G K Ghequire, Toon Swings, Jan Michiels, Susan K Buchanan, René De Mot
Lectin-like bacteriocins (LlpAs) are secreted by proteobacteria and selectively kill strains of their own or related species, and they are composed of two B-lectin domains with divergent sequences. In Pseudomonas spp., initial binding of these antibacterial proteins to cells is mediated by the carboxy-terminal domain through d-rhamnose residues present in the common polysaccharide antigen of their lipopolysaccharide, whereas the amino-terminal domain accounts for strain selectivity of killing. Here, we show that spontaneous LlpA-resistant mutants carry mutations in one of three surface-exposed moieties of the essential β-barrel outer membrane protein insertase BamA, the core component of the BAM complex...
March 20, 2018: MBio
https://www.readbyqxmd.com/read/29545539/solution-structure-of-extracellular-loop-of-human-%C3%AE-4-subunit-of-bk-channel-and-its-biological-implication-on-chtx-sensitivity
#15
Yanting Wang, Wenxian Lan, Zhenzhen Yan, Jing Gao, Xinlian Liu, Sheng Wang, Xiying Guo, Chunxi Wang, Hu Zhou, Jiuping Ding, Chunyang Cao
Large-conductance Ca2+ - and voltage-dependent K+ (BK) channels display diverse biological functions while their pore-forming α subunit is coded by a single Slo1 gene. The variety of BK channels is correlated with the effects of BKα coexpression with auxiliary β (β1-β4) subunits, as well as newly defined γ subunits. Charybdotoxin (ChTX) blocks BK channel through physically occluding the K+ -conduction pore. Human brain enriched β4 subunit (hβ4) alters the conductance-voltage curve, slows activation and deactivation time courses of BK channels...
March 15, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29531133/determinants-of-raft-partitioning-of-the-helicobacter-pylori-pore-forming-toxin-vaca
#16
Krishnan Raghunathan, Nora J Foegeding, Anne M Campbell, Timothy L Cover, Melanie D Ohi, Anne K Kenworthy
Helicobacter pylori , a Gram-negative bacterium, is a well-known risk factor for gastric cancer. H. pylori vacuolating cytotoxin A (VacA) is a secreted pore-forming toxin that induces a wide range of cellular responses. Like many other bacterial toxins, VacA has been hypothesized to utilize lipid rafts to gain entry into host cells. Here, we used giant plasma membrane vesicles (GPMVs) as a model system to understand the preferential partitioning of VacA into lipid rafts. We show that a wild-type (WT) toxin predominantly associates with the raft phase...
May 2018: Infection and Immunity
https://www.readbyqxmd.com/read/29497355/cell-free-production-of-pore-forming-toxins-functional-analysis-of-thermostable-direct-hemolysin-from-vibrio-parahaemolyticus
#17
Srujan Kumar Dondapati, Doreen A Wüstenhagen, Eckhard Strauch, Stefan Kubick
The pore forming characteristic of TDH1 and TDH2 variants of thermostable direct hemolysin (TDH), a major toxin involved in the pathogenesis of Vibrio parahaemolyticus , was studied on a planar lipid bilayer painted over individual picoliter cavities containing microelectrodes assembled in a multiarray. Both proteins formed pores upon insertion into the lipid bilayer which was shown as a shift in the conductance from the baseline current. TDH2 protein was able to produce stable currents and the currents were influenced by external factors like concentration, type of salt and voltage...
February 2018: Engineering in Life Sciences
https://www.readbyqxmd.com/read/29491391/disruption-of-the-open-conductance-in-the-%C3%AE-tongue-mutants-of-cytolysin-a
#18
Monifa A Fahie, Lucas Liang, Alzira R Avelino, Bach Pham, Patanachai Limpikirati, Richard W Vachet, Min Chen
Cytolysin A (ClyA) is a water-soluble alpha pore-forming toxin that assembles to form an oligomeric pore on host cell membranes. The ClyA monomer possesses an α-helical bundle with a β-sheet subdomain (the β-tongue) previously believed to be critical for pore assembly and/or insertion. Oligomerization of ClyA pores transforms the β-tongue into a helix-turn-helix that embeds into the lipid bilayer. Here, we show that mutations of the β-tongue did not prevent oligomerization or transmembrane insertion. Instead, β-tongue substitution mutants yielded pores with decreased conductance while a deletion mutation resulted in pores that rapidly closed following membrane association...
February 28, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29490169/uropathogenic-escherichia-coli-virulence-factor-hemolysin-a-causes-programmed-cell-necrosis-by-altering-mitochondrial-dynamics
#19
Yongning Lu, Amir Rafiq, Zhengguo Zhang, Ferial Aslani, Monika Fijak, Tao Lei, Ming Wang, Sanjeev Kumar, Jörg Klug, Martin Bergmann, Trinad Chakraborty, Andreas Meinhardt, Sudhanshu Bhushan
Uropathogenic Escherichia coli (UPEC) is the most common cause of urinary tract infections. In this study, UPEC strains harboring hemolysin A (HlyA) did not induce programmed cell death pathways by the activation of caspases. Instead, the UPEC pore-forming toxin HlyA triggered an increase in mitochondrial Ca2+ levels and manipulated mitochondrial dynamics by causing fragmentation of the mitochondrial network. Alterations in mitochondrial dynamics resulted in severe impairment of mitochondrial functions by loss of membrane potential, increase in ROS production, and ATP depletion...
February 28, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29477514/exotoxin-diversity-of-staphylococcus-aureus-isolated-from-milk-of-cows-with-subclinical-mastitis-in-central-russia
#20
K K Fursova, M P Shchannikova, I V Loskutova, A O Shepelyakovskaya, A G Laman, A M Boutanaev, S L Sokolov, O A Artem'eva, D A Nikanova, N A Zinovieva, F A Brovko
Mastitis, a major veterinary problem widespread in many regions, is caused mainly by Staphylococcus spp. However, there is no current reliable information about the role of Staphylococcus aureus and their toxins in the development of mastitis in cows in the territory of the Russian Federation. The aim of this investigation was to determine the profile of exotoxins of S. aureus from cow milk from farms of Central Russia. A total of 60 isolates of S. aureus were obtained from milk samples of cows with the subclinical form of mastitis...
May 2018: Journal of Dairy Science
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