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Pore forming toxins

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https://www.readbyqxmd.com/read/28630160/listeriolysin-o-from-bazooka-to-swiss-army-knife
#1
REVIEW
Suzanne E Osborne, John H Brumell
Listeria monocytogenes (Lm) is a Gram-positive facultative intracellular pathogen. Infections in humans can lead to listeriosis, a systemic disease with a high mortality rate. One important mechanism of Lm dissemination involves cell-to-cell spread after bacteria have entered the cytosol of host cells. Listeriolysin O (LLO; encoded by the hly gene) is a virulence factor present in Lm that plays a central role in the cell-to-cell spread process. LLO is a member of the cholesterol-dependent cytolysin (CDC) family of toxins that were initially thought to promote disease largely by inducing cell death and tissue destruction-essentially acting like a 'bazooka'...
August 5, 2017: Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
https://www.readbyqxmd.com/read/28630155/haemolytic-actinoporins-interact-with-carbohydrates-using-their-lipid-binding-module
#2
Koji Tanaka, Jose M M Caaveiro, Koldo Morante, Kouhei Tsumoto
Pore-forming toxins (PFTs) are proteins endowed with metamorphic properties that enable them to stably fold in water solutions as well as in cellular membranes. PFTs produce lytic pores on the plasma membranes of target cells conducive to lesions, playing key roles in the defensive and offensive molecular systems of living organisms. Actinoporins are a family of potent haemolytic toxins produced by sea anemones vigorously studied as a paradigm of α-helical PFTs, in the context of lipid-protein interactions, and in connection with nanopore technologies...
August 5, 2017: Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
https://www.readbyqxmd.com/read/28630151/assembly-mechanism-of-the-%C3%AE-pore-forming-toxin-cytolysin-a-from-escherichia-coli
#3
REVIEW
Daniel Roderer, Rudi Glockshuber
The cytolytic toxin cytolysin A (ClyA) from Escherichia coli is probably one of the best-characterized examples of bacterial, α-pore-forming toxins (α-PFTs). Like other PFTs, ClyA exists in a soluble, monomeric form that assembles to an annular, homo-oligomeric pore complex upon contact with detergent or target membranes. Comparison of the three-dimensional structures of the 34 kDa monomer and the protomer in the context of the dodecameric pore complex revealed that ClyA undergoes one of the largest conformational transitions described for proteins so far, in which 55% of the residues change their position and 16% of the residues adopt a different secondary structure in the protomer...
August 5, 2017: Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
https://www.readbyqxmd.com/read/28630149/molecular-mechanism-of-pore-formation-by-aerolysin-like-proteins
#4
REVIEW
Marjetka Podobnik, Matic Kisovec, Gregor Anderluh
Aerolysin-like pore-forming proteins are an important family of proteins able to efficiently damage membranes of target cells by forming transmembrane pores. They are characterized by a unique domain organization and mechanism of action that involves extensive conformational rearrangements. Although structures of soluble forms of many different members of this family are well understood, the structures of pores and their mechanism of assembly have been described only recently. The pores are characterized by well-defined β-barrels, which are devoid of any vestibular regions commonly found in other protein pores...
August 5, 2017: Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
https://www.readbyqxmd.com/read/28623231/cry6aa1-a-bacillus-thuringiensis-nematocidal-and-insecticidal-toxin-forms-pores-in-planar-lipid-bilayers-at-extremely-low-concentrations-and-without-the-need-of-proteolytic-processing
#5
Eva Fortea, Vincent Lemieux, Léna Potvin, Vimbai Chikwana, Samantha Griffin, Thimothy Hey, David McCaskill, Kenneth Narva, Sek Yee Tan, Xiaoping Xu, Vincent Vachon, Jean-Louis Schwartz
Cry6Aa1 is a Bacillus thuringiensis (Bt) toxin active against nematodes and corn rootworm insects. Its 3-D molecular structure, which has been recently elucidated, is unique among those known for other Bt toxins. Typical three-domain Bt toxins permeabilise receptor-free planar lipid bilayers (PLBs) by forming pores at doses in the 1-50 μg/ml range. Solubilisation and proteolytic activation are necessary steps for PLB permeabilisation. In contrast to other Bt toxins, Cry6Aa1 formed pores in receptor-free bilayers at doses as low as 200 pg/ml in a wide range of pH (5...
June 16, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28607368/nmr-structure-of-the-bacillus-cereus-hemolysin-ii-c-terminal-domain-reveals-a-novel-fold
#6
Anne R Kaplan, Katherine Kaus, Swastik De, Rich Olson, Andrei T Alexandrescu
In addition to multiple virulence factors, Bacillus cereus a pathogen that causes food poisoning and life-threatening wound infections, secretes the pore-forming toxin hemolysin II (HlyII). The HlyII toxin has a unique 94 amino acid C-terminal domain (HlyIIC). HlyIIC exhibits splitting of NMR resonances due to cis/trans isomerization of a single proline near the C-terminus. To overcome heterogeneity, we solved the structure of P405M-HlyIIC, a mutant that exclusively stabilizes the trans state. The NMR structure of HlyIIC reveals a novel fold, consisting of two subdomains αA-β1-β2 and β3-β4-αB-β5, that come together in a barrel-like structure...
June 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28567044/curcumin-promotes-the-clearance-of-listeria-monocytogenes-both-in-vitro-and-in-vivo-by-reducing-listeriolysin-o-oligomers
#7
Xuan Zhou, Bing Zhang, Yumei Cui, Shuiye Chen, Zihao Teng, Gejin Lu, Jianfeng Wang, Xuming Deng
The pore-forming toxin listeriolysin O (LLO), an essential virulence factor that is secreted by Listeria monocytogenes (L. monocytogenes), is responsible for bacterial breaching at the phagosomal membranes and subsequent release into the cytoplasm; it cannot be recognized by the host immune system. The vital role that LLO plays in bacterial pathogenicity and evading host immune clearance makes this virulence a promising target for addressing L. monocytogenes infection. In this study, we hypothesized that curcumin, a polyphenol derived from turmeric that could effectively inhibit LLO pore-forming activity, might be useful in the prevention or treatment of L...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28561794/antibiotic-resistance-and-virulence-phenotypes-of-recent-bacterial-strains-isolated-from-urinary-tract-infections-in-elderly-patients-with-prostatic-disease
#8
Cristina Delcaru, Paulina Podgoreanu, Ionela Alexandru, Nela Popescu, Luminiţa Măruţescu, Coralia Bleotu, George Dan Mogoşanu, Mariana Carmen Chifiriuc, Marinela Gluck, Veronica Lazăr
Acute bacterial prostatitis is one of the frequent complications of urinary tract infection (UTI). From the approximately 10% of men having prostatitis, 7% experience a bacterial prostatitis. The purpose of this study was to investigate the prevalence of uropathogens associated with UTIs in older patients with benign prostatic hyperplasia and to assess their susceptibility to commonly prescribed antibiotics as well as the relationships between microbial virulence and resistance features. Uropathogenic Escherichia coli was found to be the most frequent bacterial strain isolated from patients with benign prostatic hyperplasia, followed by Enterococcus spp...
May 31, 2017: Pathogens
https://www.readbyqxmd.com/read/28550293/stochastic-sensing-of-angiotensin-ii-with-lysenin-channels
#9
Nisha Shrestha, Sheenah L Bryant, Christopher Thomas, Devon Richtsmeier, Xinzhu Pu, Juliette Tinker, Daniel Fologea
The ability of pore-forming proteins to interact with various analytes has found vast applicability in single molecule sensing and characterization. In spite of their abundance in organisms from all kingdoms of life, only a few pore-forming proteins have been successfully reconstituted in artificial membrane systems for sensing purposes. Lysenin, a pore-forming toxin extracted from the earthworm E. fetida, inserts large conductance nanopores in lipid membranes containing sphingomyelin. Here we show that single lysenin channels may function as stochastic nanosensors by allowing the short cationic peptide angiotensin II to be electrophoretically driven through the conducting pathway...
May 26, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28546115/both-polarity-and-aromatic-ring-in-the-side-chain-of-tryptophan-246-are-involved-in-binding-activity-of-vibrio-vulnificus-hemolysin-to-target-cells
#10
Takashige Kashimoto, Tomoe Akita, Takehiro Kado, Kohei Yamazaki, Shunji Ueno
Vibrio vulnificus secretes a hemolysin/cytolysin (VVH) that induces cytolysis against a variety of mammalian cells by forming pores on the cellular membrane. VVH is known to bind to the cellular membrane as a monomer, and then convert to a pore-forming oligomer. However, the structural basis for binding of this toxin to target cells remains unknown. We show here that the polarity and indole ring on the side chain of Trp 246 (W246) of VVH, which sits on a bottom loop, participates in binding to cellular membrane...
May 22, 2017: Microbial Pathogenesis
https://www.readbyqxmd.com/read/28546029/gardnerella-vaginalis-bacteremia-associated-with-severe-acute-encephalopathy-in-a-young-female-patient
#11
Jacques Tankovic, Albertas Timinskas, Migle Janulaitiene, Milda Zilnyte, Jean-Luc Baudel, Eric Maury, Aurelija Zvirbliene, Milda Pleckaityte
Gardnerella vaginalis is a facultative anaerobic bacterium that inhabits the genitourinary tract of both healthy women and those with bacterial vaginosis. We report a case of G. vaginalis bacteremia associated with severe toxic encephalopathy in a young woman. Anaerobic blood cultures yielded pure growth of small gram-variable rods later identified as G. vaginalis by both rapid biochemical tests and 16S rRNA gene sequencing. The patient recovered after treatment with amoxicillin-clavulanate according to the in vitro susceptibility testing...
May 22, 2017: Anaerobe
https://www.readbyqxmd.com/read/28545305/clostridium-difficile-toxins-a-and-b-receptors-pores-and-translocation-into-cells
#12
Kathleen E Orrell, Zhifen Zhang, Seiji N Sugiman-Marangos, Roman A Melnyk
The most potent toxins secreted by pathogenic bacteria contain enzymatic moieties that must reach the cytosol of target cells to exert their full toxicity. Toxins such as anthrax, diphtheria, and botulinum toxin all use three well-defined functional domains to intoxicate cells: a receptor-binding moiety that triggers endocytosis into acidified vesicles by binding to a specific host-cell receptor, a translocation domain that forms pores across the endosomal membrane in response to acidic pH, and an enzyme that translocates through these pores to catalytically inactivate an essential host cytosolic substrate...
May 26, 2017: Critical Reviews in Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28544414/effective-low-cost-recovery-of-toxic-arsenate-anions-from-water-using-hollow-sphere-trapper-geodes
#13
Sherif A El-Safty, Mohamed A Shenashen, Naeem Akhtar, Mahmoud M Selim, Wafaa M Morsy, Hitoshi Yamaguchi, Satoshi Kawada, Abdulaziz A Alhamid, Naoki Ohashi, Izumi Ichinose, Ahmed Alamoudi
Because of the devastating impacts of arsenic to terrestrial and aquatic organisms, recovery, removal, disposal and management of arsenic-contaminated water has a considerable challenge and become an urgent necessity in the field of water treatment. This study reports control fabrication of low-cost adsorbents based on microscopic NiO hollow sphere geode-shelled a 100 nm of poly-CN nano-sphere particles-like nodules of poly-carbon nitride that intrinsically stacked and wrapped around the hollow nest spheres to form 500-700 nm shell...
May 22, 2017: Chemistry, An Asian Journal
https://www.readbyqxmd.com/read/28539590/abcc2-is-associated-with-bacillus-thuringiensis-cry1ac-toxin-oligomerization-and-membrane-insertion-in-diamondback-moth
#14
Josue Ocelotl, Jorge Sánchez, Isabel Gómez, Bruce E Tabashnik, Alejandra Bravo, Mario Soberón
Cry1A insecticidal toxins bind sequentially to different larval gut proteins facilitating oligomerization, membrane insertion and pore formation. Cry1Ac interaction with cadherin triggers oligomerization. However, a mutation in an ABC transporter gene (ABCC2) is linked to Cry1Ac resistance in Plutella xylostella. Cry1AcMod, engineered to lack helix α-1, was able to form oligomers without cadherinbinding and effectively countered Cry1Ac resistance linked to ABCC2. Here we analyzed Cry1Ac and Cry1AcMod binding and oligomerization by western blots using brush border membrane vesicles (BBMV) from a strain of P...
May 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28537279/synthesis-of-biotin-labelled-core-glycans-of-gpi-anchors-and-their-application-in-the-study-of-gpi-interaction-with-pore-forming-bacterial-toxins
#15
Jian Gao, Zhifang Zhou, Jiatong Guo, Zhongwu Guo
A convergent strategy was developed for the first-time synthesis of biotin-labeled GPI core glycans. These GPI conjugates are useful for various biological studies showcased by their application in the scrutiny of pore-forming bacterial toxin-GPI interaction, revealing that the phosphate group at the GPI inositol 1-O-position had a significant impact on GPI-toxin binding.
June 6, 2017: Chemical Communications: Chem Comm
https://www.readbyqxmd.com/read/28533492/anti-tumor-activity-of-anthrax-toxin-variants-that-form-a-functional-translocation-pore-by-intermolecular-complementation
#16
Shihui Liu, Qian Ma, Rasem Fattah, Thomas H Bugge, Stephen H Leppla
Anthrax lethal toxin is a typical A-B type protein toxin secreted by Bacillus anthracis. Lethal factor (LF) is the catalytic A-subunit, a metalloprotease having MEKs as targets. LF relies on the cell-binding B-subunit, protective antigen (PA), to gain entry into the cytosol of target cells. PA binds to cell surface toxin receptors and is activated by furin protease to form an LF-binding-competent oligomer-PA pre-pore, which converts to a functional protein-conductive pore in the acidic endocytic vesicles, allowing translocation of LF into the cytosol...
May 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28526816/delineation-of-b-cell-epitopes-of-salmonella-enterica-serovar-typhi-hemolysin-e-potential-antibody-therapeutic-target
#17
Chai Fung Chin, Jing Yi Lai, Yee Siew Choong, Amy Amilda Anthony, Asma Ismail, Theam Soon Lim
Hemolysin E (HlyE) is an immunogenic novel pore-forming toxin involved in the pathogenesis of typhoid fever. Thus, mapping of B-cell epitopes of Salmonella enterica serovar Typhi (S. Typhi) is critical to identify key immunogenic regions of HlyE. A random 20-mer peptide library was used for biopanning with enriched anti-HlyE polyclonal antibodies from typhoid patient sera. Bioinformatic tools were used to refine, analyze and map the enriched peptide sequences against the protein to identify the epitopes. The analysis identified both linear and conformational epitopes on the HlyE protein...
May 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28522850/pseudomonas-aeruginosa-exolysin-promotes-bacterial-growth-in-lungs-alveolar-damage-and-bacterial-dissemination
#18
Stéphanie Bouillot, Patrick Munro, Benoit Gallet, Emeline Reboud, François Cretin, Guillaume Golovkine, Guy Schoehn, Ina Attrée, Emmanuel Lemichez, Philippe Huber
Exolysin (ExlA) is a recently-identified pore-forming toxin secreted by a subset of Pseudomonas aeruginosa strains identified worldwide and devoid of Type III secretion system (T3SS), a major virulence factor. Here, we characterized at the ultrastructural level the lesions caused by an ExlA-secreting strain, CLJ1, in mouse infected lungs. CLJ1 induced necrotic lesions in pneumocytes and endothelial cells, resulting in alveolo-vascular barrier breakdown. Ectopic expression of ExlA in an exlA-negative strain induced similar tissue injuries...
May 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28516064/a-novel-role-of-listeria-monocytogenes-membrane-vesicles-in-inhibition-of-autophagy-and-cell-death
#19
Svitlana Vdovikova, Morten Luhr, Paula Szalai, Lars Nygård Skalman, Monika K Francis, Richard Lundmark, Nikolai Engedal, Jörgen Johansson, Sun N Wai
Bacterial membrane vesicle (MV) production has been mainly studied in Gram-negative species. In this study, we show that Listeria monocytogenes, a Gram-positive pathogen that causes the food-borne illness listeriosis, produces MVs both in vitro and in vivo. We found that a major virulence factor, the pore-forming hemolysin listeriolysin O (LLO), is tightly associated with the MVs, where it resides in an oxidized, inactive state. Previous studies have shown that LLO may induce cell death and autophagy. To monitor possible effects of LLO and MVs on autophagy, we performed assays for LC3 lipidation and LDH sequestration as well as analysis by confocal microscopy of HEK293 cells expressing GFP-LC3...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28505109/the-vip3ag4-insecticidal-protoxin-from-bacillus-thuringiensis-adopts-a-tetrameric-configuration-that-is-maintained-on-proteolysis
#20
Leopoldo Palma, David J Scott, Gemma Harris, Salah-Ud Din, Thomas L Williams, Oliver J Roberts, Mark T Young, Primitivo Caballero, Colin Berry
The Vip3 proteins produced during vegetative growth by strains of the bacterium Bacillus thuringiensis show insecticidal activity against lepidopteran insects with a mechanism of action that may involve pore formation and apoptosis. These proteins are promising supplements to our arsenal of insecticidal proteins, but the molecular details of their activity are not understood. As a first step in the structural characterisation of these proteins, we have analysed their secondary structure and resolved the surface topology of a tetrameric complex of the Vip3Ag4 protein by transmission electron microscopy...
May 14, 2017: Toxins
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