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Pore forming toxins

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https://www.readbyqxmd.com/read/27919210/three-dimensional-modelling-of-the-voltage-gated-sodium-ion-channel-from-anopheles-gambiae-reveals-spatial-clustering-of-evolutionarily-conserved-acidic-residues-at-the-extracellular-sites
#1
Rithvik S Vinekar, Ramanathan Sowdhamini
The eukaryotic voltage-gated sodium channel(e-Nav) is a large asymmetric transmembrane protein with important functions concerning neurological function. No structure has been resolved at high resolution for this protein. A homology model of the transmembrane and extracellular regions of an Anopheles gambiae para-like channel with emphasis on the pore entrance has been constructed, based upon the templates provided by a prokaryotic sodium channel and a potassium two-pore channel. The latter provides a template for the extracellular regions, which are located above the entrance to the pore, which is likely to open at a side of a dome formed by these loops...
December 5, 2016: Current Neuropharmacology
https://www.readbyqxmd.com/read/27918112/validation-of-adam10-metalloprotease-as-a-bacillus-thuringiensis-cry3aa-toxin-functional-receptor-in-colorado-potato-beetle-leptinotarsa-decemlineata
#2
V M Ruiz-Arroyo, I García-Robles, C Ochoa-Campuzano, G A Goig, E Zaitseva, G Baaken, A C Martínez-Ramírez, C Rausell, M D Real
Bacillus thuringiensis parasporal crystal proteins (Cry proteins) are insecticidal pore-forming toxins that bind to specific receptor molecules on the brush border membrane of susceptible insect midgut cells to exert their toxic action. In the Colorado potato beetle (CPB), a coleopteran pest, we previously proposed that interaction of Cry3Aa toxin with a CPB ADAM10 metalloprotease is an essential part of the mode of action of this toxin. Here, we annotated the gene sequence encoding an ADAM10 metalloprotease protein (CPB-ADAM10) in the CPB genome sequencing project, and using RNA interference gene silencing we demonstrated that CPB-ADAM10 is a Cry3Aa toxin functional receptor in CPB...
December 5, 2016: Insect Molecular Biology
https://www.readbyqxmd.com/read/27914761/lactobacillus-iners-friend-or-foe
#3
REVIEW
Mariya I Petrova, Gregor Reid, Mario Vaneechoutte, Sarah Lebeer
The vaginal microbial community is typically characterized by abundant lactobacilli. Lactobacillus iners, a fairly recently detected species, is frequently present in the vaginal niche. However, the role of this species in vaginal health is unclear, since it can be detected in normal conditions as well as during vaginal dysbiosis, such as bacterial vaginosis, a condition characterized by an abnormal increase in bacterial diversity and lack of typical lactobacilli. Compared to other Lactobacillus species, L...
November 30, 2016: Trends in Microbiology
https://www.readbyqxmd.com/read/27910935/disentangling-the-roles-of-cholesterol-and-cd59-in-intermedilysin-pore-formation
#4
Courtney M Boyd, Edward S Parsons, Richard A G Smith, John M Seddon, Oscar Ces, Doryen Bubeck
The plasma membrane provides an essential barrier, shielding a cell from the pressures of its external environment. Pore-forming proteins, deployed by both hosts and pathogens alike, breach this barrier to lyse target cells. Intermedilysin is a cholesterol-dependent cytolysin that requires the human immune receptor CD59, in addition to cholesterol, to form giant β-barrel pores in host membranes. Here we integrate biochemical assays with electron microscopy and atomic force microscopy to distinguish the roles of these two receptors in mediating structural transitions of pore formation...
December 2, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27900629/dracorhodin-perochlorate-attenuates-staphylococcus-aureus-usa300-virulence-by-decreasing-%C3%AE-toxin-expression
#5
Yumin Liu, Dongxue Shi, Yan Guo, Meng Li, Yonghong Zha, Quankai Wang, Jianfeng Wang
α-Toxin, a pore-forming toxin secreted by most Staphylococcus aureus, plays critical role in the pathogenesis associated with various infectious diseases. The USA300 which is a major international epidemic methicilin-resisrant S. aureus has spread rapidly to multiple countries and become an emerging public health concern. In this study, the in vitro efficacy of Dracorhodin Perochlorate (DP) against USA300 virulence was evaluated. Using susceptibility testing, immunoblots, rabbit blood haemolytic assay and real-time RT-PCR, we observed that the α-toxin production was decreased when USA300 was co-cultured with different sub-inhibitory concentration of DP...
January 2017: World Journal of Microbiology & Biotechnology
https://www.readbyqxmd.com/read/27892542/streptococcus-pneumoniae-disrupts-pulmonary-immune-defence-via-elastase-release-following-pneumolysin-dependent-neutrophil-lysis
#6
Hisanori Domon, Masataka Oda, Tomoki Maekawa, Kosuke Nagai, Wataru Takeda, Yutaka Terao
Streptococcus pneumoniae is a leading cause of bacterial pneumonia and is the principal cause of morbidity and mortality worldwide. Previous studies suggested that excessive activation of neutrophils results in the release of neutrophil elastase, which contributes to lung injury in severe pneumonia. Although both pneumococcal virulence factors and neutrophil elastase contribute to the development and progression of pneumonia, there are no studies analysing relationships between these factors. Here, we showed that pneumolysin, a pneumococcal pore-forming toxin, induced cell lysis in primary isolated human neutrophils, leading to the release of neutrophil elastase...
November 28, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27889464/enterocyte-purge-and-rapid-recovery-is-a-resilience-reaction-of-the-gut-epithelium-to-pore-forming-toxin-attack
#7
Kwang-Zin Lee, Matthieu Lestradet, Catherine Socha, Stefanie Schirmeier, Antonin Schmitz, Caroline Spenlé, Olivier Lefebvre, Céline Keime, Wennida M Yamba, Richard Bou Aoun, Samuel Liegeois, Yannick Schwab, Patricia Simon-Assmann, Frédéric Dalle, Dominique Ferrandon
Besides digesting nutrients, the gut protects the host against invasion by pathogens. Enterocytes may be subjected to damage by both microbial and host defensive responses, causing their death. Here, we report a rapid epithelial response that alleviates infection stress and protects the enterocytes from the action of microbial virulence factors. Intestinal epithelia exposed to hemolysin, a pore-forming toxin secreted by Serratia marcescens, undergo an evolutionarily conserved process of thinning followed by the recovery of their initial thickness within a few hours...
November 12, 2016: Cell Host & Microbe
https://www.readbyqxmd.com/read/27886001/strategy-for-the-hemocompatibility-testing-of-microparticles
#8
S Braune, S Basu, K Kratz, J Bäckemo Johansson, M Reinthaler, A Lendlein, F Jung
Polymer-based microparticles are applied as non-thrombogenic or thrombogenic materials in a wide variety of intra- or extra-corporeal medical devices. As demanded by the regulatory agencies, the hemocompatibility of these blood contacting biomaterials has to be evaluated in vitro to ensure that the particle systems appropriately fulfill the envisioned function without causing undesired events such as thrombosis or inflammation. Currently described in vitro assays for hemocompatibility testing of particles comprise tests with different single cell types (e...
November 23, 2016: Clinical Hemorheology and Microcirculation
https://www.readbyqxmd.com/read/27875098/hlh-30-tfeb-mediated-autophagy-functions-in-a-cell-autonomous-manner-for-epithelium-intrinsic-cellular-defense-against-bacterial-pore-forming-toxin-in-c-elegans
#9
Huan-Da Chen, Cheng-Yuan Kao, Bang-Yu Liu, Shin-Whei Huang, Cheng-Ju Kuo, Jhen-Wei Ruan, Yen-Hung Lin, Cheng-Rung Huang, Yu-Hung Chen, Horng-Dar Wang, Raffi V Aroian, Chang-Shi Chen
Autophagy is an evolutionarily conserved intracellular system that maintains cellular homeostasis by degrading and recycling damaged cellular components. The transcription factor HLH-30/TFEB-mediated autophagy has been reported to regulate tolerance to bacterial infection, but less is known about the bona fide bacterial effector that activates HLH-30 and autophagy. Here, we unveil that bacterial membrane pore-forming toxin (PFT) induces autophagy in an HLH-30-dependent manner in Caenorhabditis elegans. Moreover, autophagy controls the susceptibility of animals to PFT toxicity through xenophagic degradation of PFT and repair of membrane-pore cell-autonomously in the PFT-targeted intestinal cells in C...
November 22, 2016: Autophagy
https://www.readbyqxmd.com/read/27864644/targeting-and-alteration-of-tight-junctions-by-bacteria-and-their-virulence-factors-such-as-clostridium-perfringens-enterotoxin
#10
REVIEW
Miriam Eichner, Jonas Protze, Anna Piontek, Gerd Krause, Jörg Piontek
The integrity of tight junctions, which regulate paracellular permeability, is challenged by many bacterial pathogens. This is caused by inflammatory responses triggered by pathogens and direct interaction of bacteria or their toxins with host epithelial cells. In some cases, tight junction proteins represent receptors for cell surface proteins or toxins of the pathogen, such as Clostridium perfringens enterotoxin (CPE). CPE causes diarrhea and cramps-the symptoms of a common foodborne illness, caused by C...
November 18, 2016: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/27847174/protective-efficacy-of-a-novel-alpha-hemolysin-subunit-vaccine-at62-against-staphylococcus-aureus-skin-and-soft-tissue-infections
#11
Rajan P Adhikari, Christopher D Thompson, M Javad Aman, Jean C Lee
Alpha hemolysin (Hla) is a pore-forming toxin produced by most Staphylococcus aureus isolates. Hla is reported to play a key role in the pathogenesis of staphylococcal infections, such as skin and soft tissue infection, pneumonia, and lethal peritonitis. This study makes use of a novel recombinant subunit vaccine candidate (AT62) that was rationally designed based on the Hla heptameric crystal structure. AT62 comprises a critical structural domain at the N terminus of Hla, and it has no inherent toxic properties...
December 7, 2016: Vaccine
https://www.readbyqxmd.com/read/27819327/structure-and-function-of-fs50-a-salivary-protein-from-the-flea-xenopsylla-cheopis-that-blocks-the-sodium-channel-nav1-5
#12
Xueqing Xu, Bei Zhang, Shilong Yang, Su An, José M C Ribeiro, John F Andersen
Naturally occurring toxins have been invaluable tools for the study of structural and functional relationships of voltage-gated sodium channels (VGSC). Few studies have been made of potential channel-modulating substances from blood-feeding arthropods. He we describe the characterization FS50, a salivary protein from the flea, Xenopsylla cheopis, that exhibits an inhibitory activity against the NaV1.5 channel with an IC50 of 1.58 μM. The pore-blocking mechanism of this toxin is evident from the kinetics of activation and inactivation suggesting that FS50 does not interfere with the voltage sensor of NaV1...
November 7, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27807200/molecular-determinants-of-bk-channel-functional-diversity-and-functioning
#13
REVIEW
Ramon Latorre, Karen Castillo, Willy Carrasquel-Ursulaez, Romina V Sepulveda, Fernando Gonzalez-Nilo, Carlos Gonzalez, Osvaldo Alvarez
Large-conductance Ca(2+)- and voltage-activated K(+) (BK) channels play many physiological roles ranging from the maintenance of smooth muscle tone to hearing and neurosecretion. BK channels are tetramers in which the pore-forming α subunit is coded by a single gene (Slowpoke, KCNMA1). In this review, we first highlight the physiological importance of this ubiquitous channel, emphasizing the role that BK channels play in different channelopathies. We next discuss the modular nature of BK channel-forming protein, in which the different modules (the voltage sensor and the Ca(2+) binding sites) communicate with the pore gates allosterically...
January 2017: Physiological Reviews
https://www.readbyqxmd.com/read/27797514/capturing-the-membrane-triggered-conformational-transition-of-an-%C3%AE-helical-pore-forming-toxin
#14
V V Hemanth Giri Rao, Rajat Desikan, K Ganapathy Ayappa, Shachi Gosavi
E. coli Cytolysin A (ClyA) is an α-helical pore forming toxin (PFT) which lyses target cells by forming membrane permeabilizing pores. The rate determining step of this process is the conversion of the soluble ClyA monomer into a membrane inserted protomer. We elucidate the mechanism of this conformational transition using molecular dynamics simulations of coarse-grained models of ClyA and a membrane. We find that a membrane is necessary for the conformational conversion because membrane-protein interactions counteract the loss of the many intra-protein hydrophobic interactions that stabilize the membrane-inserting segments in the ClyA monomer...
October 31, 2016: Journal of Physical Chemistry. B
https://www.readbyqxmd.com/read/27784764/disulphide-bond-restrains-c-terminal-region-of-thermostable-direct-hemolysin-during-folding-to-promote-oligomerization
#15
Nidhi Kundu, Swapnil Tichkule, Shashi Bhushan Pandit, Kausik Chattopadhyay
Pore-forming toxins (PFTs) are typically produced as water-soluble monomers, which upon interacting with the target cells assemble into transmembrane oligomeric pores. Vibrio parahaemolyticus thermostable direct hemolysin (TDH) is an atypical PFT that exists as tetramer in solution, prior to its membrane-binding. TDH structure highlights a core beta-sandwich domain similar to those found in the eukaryotic actinoporin family of PFTs. However, TDH structure harbors an extended C-terminal region (CTR) that is not documented in the actinoporins...
October 26, 2016: Biochemical Journal
https://www.readbyqxmd.com/read/27776114/wheat-fhb1-encodes-a-chimeric-lectin-with-agglutinin-domains-and-a-pore-forming-toxin-like-domain-conferring-resistance-to-fusarium-head-blight
#16
Nidhi Rawat, Michael O Pumphrey, Sixin Liu, Xiaofei Zhang, Vijay K Tiwari, Kaori Ando, Harold N Trick, William W Bockus, Eduard Akhunov, James A Anderson, Bikram S Gill
Fusarium head blight (FHB), caused by Fusarium graminearum, is a devastating disease of wheat and barley that leads to reduced yield and mycotoxin contamination of grain, making it unfit for human consumption. FHB is a global problem, with outbreaks in the United States, Canada, Europe, Asia and South America. In the United States alone, total direct and secondary economic losses from 1993 to 2001 owing to FHB were estimated at $7.67 billion. Fhb1 is the most consistently reported quantitative trait locus (QTL) for FHB resistance breeding...
October 24, 2016: Nature Genetics
https://www.readbyqxmd.com/read/27769815/parasporins-1-and-2-their-structure-and-activity
#17
Toshihiko Akiba, Shiro Okumura
Parasporins are novel protein toxins preferentially cytotoxic against human cancer cells. They are obtained from parasporal inclusions of Bacillus thuringiensis and, accordingly, are considered congeners of the insecticidal Cry toxins. Two types of parasporins have been identified: the three-domain Cry toxin type and the β-pore-forming-toxin (β-PFT) type. Crystal structures of representative members of the two types, PS1Aa1 and PS2Aa1, have been determined and compared with those of well-studied toxins. PS1Aa1 has a typical architecture characteristic of the three-domain insecticidal Cry toxins, though it is cleaved into two polypeptides...
October 18, 2016: Journal of Invertebrate Pathology
https://www.readbyqxmd.com/read/27762484/-non-haemolytic-enterotoxin-nhe-of-bacillus-cereus-induces-apoptosis-in-vero-cells
#18
Xiaoye Liu, Shuangyang Ding, Peijie Shi, Richard Dietrich, Erwin Märtlbauer, Kui Zhu
Bacillus cereus is an opportunistic pathogen that often causes foodborne infectious diseases and food poisoning. Non-haemolytic enterotoxin (Nhe) is the major toxin found in almost all enteropathogenic B. cereus and B. thuringiensis isolates. However, little is known about the cellular response after Nhe triggered pore formation on cell membrane. Here we demonstrate that Nhe induced cell cycle arrest at G0 /G1 phase and provoked apoptosis in Vero cells, most likely associated with mitogen-activated protein kinase (MAPK) and death receptor pathways...
October 20, 2016: Cellular Microbiology
https://www.readbyqxmd.com/read/27756538/block-of-voltage-gated-calcium-channels-by-peptide-toxins
#19
Emmanuel Bourinet, Gerald W Zamponi
Venoms from various predatory species, such as fish hunting mollusks scorpions, snakes and arachnids contain a large spectrum of toxins that include blockers of voltage-gated calcium channels. These peptide blockers act by two principal manners - physical occlusion of the pore and prevention of activation gating. Many of the calcium channel-blocking peptides have evolved to tightly occupy their binding pocket on the principal pore forming subunit of the channel, often rendering block poorly reversible. Moreover, several of the best characterized blocking peptides have developed a high degree of channel subtype selectivity...
October 15, 2016: Neuropharmacology
https://www.readbyqxmd.com/read/27740593/pectocin-m1-pcam1-inhibits-escherichia-coli-cell-growth-and-peptidoglycan-biosynthesis-through-periplasmic-expression
#20
Dimitri Chérier, Sean Giacomucci, Delphine Patin, Ahmed Bouhss, Thierry Touzé, Didier Blanot, Dominique Mengin-Lecreulx, Hélène Barreteau
Colicins are bacterial toxins produced by some Escherichia coli strains. They exhibit either enzymatic or pore-forming activity towards a very limited number of bacterial species, due to the high specificity of their reception and translocation systems. Yet, we succeeded in making the colicin M homologue from Pectobacterium carotovorum, pectocin M1 (PcaM1), capable of inhibiting E. coli cell growth by bypassing these reception and translocation steps. This goal was achieved through periplasmic expression of this pectocin...
October 8, 2016: Antibiotics
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