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Bacterial exotoxin

P Chellapandi, A Prisilla
Clostridium botulinum group III strains are able to produce cytotoxins, C2 toxin and C3 exotoxin, along with botulinum neurotoxin types C and D. C2 toxin and C3 exotoxin produced from this organism are the most important members of bacterial ADP-ribosyltransferase superfamily. Both toxins have distinct pathophysiological functions in the avian and mammalian hosts. The members of this superfamily transfer an ADP-ribose moiety of NAD+ to specific eukaryotic target proteins. The present review describes the structure, function and evolution aspects of these toxins with a special emphasis to the development of veterinary vaccines...
December 1, 2016: Current Protein & Peptide Science
Marta Borowiec, Michal Gorzkiewicz, Joanna Grzesik, Aurelia Walczak-Drzewiecka, Anna Salkowska, Ewelina Rodakowska, Kamil Steczkiewicz, Leszek Rychlewski, Jaroslaw Dastych, Krzysztof Ginalski
Exotoxin A (PE) from Pseudomonas aeruginosa is a bacterial ADP-ribosyltransferase, which can permanently inhibit translation in the attacked cells. Consequently, this toxin is frequently used in immunotoxins for targeted cancer therapies. In this study, we propose a novel modification to PE by incorporating the NLS sequence at its C-terminus, to make it a selective agent against fast-proliferating cancer cells, as a nucleus-accumulated toxin should be separated from its natural substrate (eEF2) in slowly dividing cells...
November 10, 2016: Toxins
Thomas G Blanchard, Steven J Czinn
Establishment of Helicobacter pylori infection as an etiologic agent of peptic ulcer disease and other gastric pathologies marked a revolution in gastroenterology which spurred an enormous interest in gastric physiology and immunology research. The association was soon also demonstrated in children as well. Application of antimicrobial therapies have proven remarkably efficacious in eradicating H. pylori and curing pediatric patients of duodenal ulcers as well as gastritis, negating a lifetime of ineffective therapy and life-threatening disease...
October 4, 2016: Pediatric Research
William Leonardi, Leeor Zilbermintz, Luisa W Cheng, Josue Zozaya, Sharon H Tran, Jeffrey H Elliott, Kseniya Polukhina, Robert Manasherob, Amy Li, Xiaoli Chi, Dima Gharaibeh, Tara Kenny, Rouzbeh Zamani, Veronica Soloveva, Andrew D Haddow, Farooq Nasar, Sina Bavari, Michael C Bassik, Stanley N Cohen, Anastasia Levitin, Mikhail Martchenko
Diverse pathogenic agents often utilize overlapping host networks, and hub proteins within these networks represent attractive targets for broad-spectrum drugs. Using bacterial toxins, we describe a new approach for discovering broad-spectrum therapies capable of inhibiting host proteins that mediate multiple pathogenic pathways. This approach can be widely used, as it combines genetic-based target identification with cell survival-based and protein function-based multiplex drug screens, and concurrently discovers therapeutic compounds and their protein targets...
September 30, 2016: Scientific Reports
Inka Sastalla, Denise M Monack, Katharina F Kubatzky
No abstract text is available yet for this article.
2016: Frontiers in Immunology
Soha El-Shaer, Mona Shaaban, Rasha Barwa, Ramadan Hassan
The spread of multidrug-resistant Pseudomonas aeruginosa isolates constitutes a serious clinical challenge. Bacterial efflux machinery is a crucial mechanism of resistance among P. aeruginosa. Efflux inhibitors such as phenylalanine arginyl β-naphthylamide (PAβN) promote the bacterial susceptibility to antimicrobial agents. The pathogenesis of P. aeruginosa is coordinated via quorum sensing (QS). This study aims to find out the impact of efflux pump inhibitor, PAβN, on QS and virulence attributes in clinical isolates of P...
October 2016: Journal of Medical Microbiology
Goli Yamini, Ekaterina M Nestorovich
Rational design of multivalent molecules represents a remarkable modern tool to transform weak non-covalent interactions into strong binding by creating multiple finely-tuned points of contact between multivalent ligands and their supposed multivalent targets. Here, we describe several prominent examples where the multivalent blockers were investigated for their ability to directly obstruct oligomeric channel-forming bacterial exotoxins, such as the pore-forming bacterial toxins and B component of the binary bacterial toxins...
July 29, 2016: Current Topics in Microbiology and Immunology
Chinni Yalamanchili, Vamshi K Manda, Amar G Chittiboyina, Rebecca L Guernieri, William A Harrell, Robert P Webb, Leonard A Smith, Ikhlas A Khan
ETHNOPHARMACOLOGICAL RELEVANCE: Ayurveda, an ancient holistic system of health care practiced on the Indian subcontinent, utilizes a number of multi-plant formulations and is considered by many as a potential source for novel treatments, as well as the identification of new drugs. Our aim is to identify novel phytochemicals for the inhibition of bacterial exotoxin, botulinum neurotoxin A (BoNT/A) based on Ayurvedic literature. BoNT/A is released by Clostridium species, which when ingested, inhibits the release of acetylcholine by concentrating at the neuromuscular junction and causes flaccid paralysis, resulting in a condition termed as botulism, and may also lead to death due to respiratory arrest...
July 25, 2016: Journal of Ethnopharmacology
Gilad Kaplan, Fred Lee, Masanori Onda, Emily Kolyvas, Gaurav Bhardwaj, David Baker, Ira Pastan
Recombinant immunotoxins (RITs) are fusions of an Fv-based targeting moiety and a toxin. Pseudomonas exotoxin A (PE) has been used to make several immunotoxins that have been evaluated in clinical trials. Immunogenicity of the bacterial toxin and off-target toxicity have limited the efficacy of these immunotoxins. To address these issues, we have previously made RITs in which the Fv is connected to domain III (PE24) by a furin cleavage site (FCS), thereby removing unneeded sequences of domain II. However, the PE24 containing RITs do not contain the naturally occurring disulfide bond around the furin cleavage sequence, because it was removed when domain II was deleted...
2016: Toxins
Timothy E G Ferguson, James A Reihill, Brian Walker, Robert A Hamilton, S Lorraine Martin
Many bacterial and viral pathogens (or their toxins), including Pseudomonas aeruginosa exotoxin A, require processing by host pro-protein convertases such as furin to cause disease. We report the development of a novel irreversible inhibitor of furin (QUB-F1) consisting of a diphenyl phosphonate electrophilic warhead coupled with a substrate-like peptide (RVKR), that also includes a biotin tag, to facilitate activity-based profiling/visualisation. QUB-F1 displays greater selectivity for furin, in comparison to a widely used exemplar compound (furin I) which has a chloromethylketone warhead coupled to RVKR, when tested against the serine trypsin-like proteases (trypsin, prostasin and matriptase), factor Xa and the cysteine protease cathepsin B...
2016: PloS One
Soni Kaundal, Manju Uttam, Krishan Gopal Thakur
Contact dependent growth inhibition (CDI) is the phenomenon where CDI+ bacterial strain (inhibitor) inhibits the growth of CDI-strain (target) by direct cell to cell contact. CDI is mediated by cdiBAI gene cluster where CdiB facilitates the export of CdiA, an exotoxin, on the cell surface and CdiI acts as an immunity protein to protect CDI+ cells from autoinhibition. CdiA-CT, the C-terminal region of the toxin CdiA, from uropathogenic Escherichia coli strain 536 (UPEC536) is a latent tRNase that requires binding of a biosynthetic enzyme CysK (O-acetylserine sulfyhydrylase) for activation in the target cells...
2016: PloS One
Sameh Sellami, Sonia Jemli, Nouha Abdelmalek, Emna Dabbéche, Kaïs Jamoussi
The Bacillus thuringiensis S1/4 strain was previously found to harbour vip1S, vip2S, and vip3 genes. Its plasmid curing led to the obtaining of four partially cured strains S1/4-2, S1/4-3, S1/4-7, and S1/4-9 (vip2S-vip1S (-), vip3 (+)), one strain S1/4-4 (vip2S-vip1S (+), vip3 (-)), and S1/4-0 strain lacking the three genes. Using these derivative strains as templates, PCR amplification and southern blot assay revealed that vip2S-vip1S operon and vip3 gene were localized on two different large plasmids. Bioinformatics studies showed that vip2S (1...
October 2016: International Journal of Biological Macromolecules
Toshio Shibata, Kouki Maki, Jinki Hadano, Takumi Fujikawa, Kazuki Kitazaki, Takumi Koshiba, Shun-Ichiro Kawabata
[This corrects the article DOI: 10.1371/journal.ppat.1005244.].
June 2016: PLoS Pathogens
Chia-Ling Chen, Yueh-Ying Wu, Chiou-Feng Lin, Chih-Feng Kuo, Chia-Li Han, Shuying Wang, Woei-Jer Chuang, Chiu-Yueh Chen, Jiunn-Jong Wu, Pei-Jane Tsai, Ching-Chuan Liu, Yee-Shin Lin
Clearance of apoptotic cells by macrophages plays an important role in maintaining tissue homeostasis. Previous study indicated that streptococcal pyrogenic exotoxin B (SPE B) reduces phagocytic activity in group A streptococcus (GAS) infection. Here, we demonstrate that SPE B causes an inhibitory effect on protein S-mediated phagocytosis. In the presence of SPE B, serum- and purified protein S-mediated phagocytosis of apoptotic cells were significantly inhibited. The binding abilities of protein S to apoptotic cells were decreased by treatment with SPE B...
2016: Scientific Reports
Vigneshkumar Balasubramanian, Durai Sellegounder, Kundu Suman, Balamurugan Krishnaswamy
UNLABELLED: Caenorhabditis elegans-Pseudomonas aeruginosa infection model is commonly used for pathogenesis studies over the decades. In the present study, upon exposure to the Pseudomonas aeruginosa PAO1, the 2D-PAGE was performed to examine the total proteins differences of C. elegans during the PAO1 infection at different time durations (12-48h). Also, the 2D-DIGE using the cyanine dyes were performed (48h) to identify the differentially regulated proteins against the PAO1 infection...
August 11, 2016: Journal of Proteomics
Tamara Martinović, Uroš Andjelković, Martina Šrajer Gajdošik, Dina Rešetar, Djuro Josić
UNLABELLED: Foodborne pathogens, mostly bacteria and fungi, but also some viruses, prions and protozoa, contaminate food during production and processing, but also during storage and transport before consuming. During their growth these microorganisms can secrete different components, including toxins, into the extracellular environment. Other harmful substances can be also liberated and can contaminate food after disintegration of food pathogens. Some bacterial and fungal toxins can be resistant to inactivation, and can survive harsh treatment during food processing...
September 16, 2016: Journal of Proteomics
Maren von Köckritz-Blickwede, Stefanie Blodkamp, Victor Nizet
Since their discovery in 2004, neutrophil extracellular traps (NETs) have been characterized as a fundamental host innate immune defense against various pathogens. Released in response to infectious and pro-inflammatory stimuli, NETs can immobilize invading pathogens within a fibrous matrix consisting of DNA, histones, and antimicrobial peptides. Conversely, excessive or dysregulated NET release may hold a variety of detrimental consequences for the host. A fine balance between NET formation and elimination is necessary to sustain a protective effect during infectious challenge...
2016: Frontiers in Microbiology
Nicole Reisinger, Ilse Dohnal, Veronika Nagl, Simone Schaumberger, Gerd Schatzmayr, Elisabeth Mayer
One of the most important hoof diseases is laminitis. Yet, the pathology of laminitis is not fully understood. Different bacterial toxins, e.g. endotoxins or exotoxins, seem to play an important role. Additionally, ingestion of mycotoxins, toxic secondary metabolites of fungi, might contribute to the onset of laminitis. In this respect, fumonsins are of special interest since horses are regarded as species most susceptible to this group of mycotoxins. The aim of our study was to investigate the influence of fumonisin B₁ (FB₁) on primary isolated epidermal and dermal hoof cells, as well as on the lamellar tissue integrity and sphingolipid metabolism of hoof explants in vitro...
April 2016: Toxins
James A Reihill, Brian Walker, Robert A Hamilton, Timothy E G Ferguson, J Stuart Elborn, M Jackson Stutts, Brian J Harvey, Vinciane Saint-Criq, Siobhan M Hendrick, S Lorraine Martin
RATIONALE: In cystic fibrosis (CF) a reduction in airway surface liquid (ASL) height compromises mucociliary clearance, favoring mucus plugging and chronic bacterial infection. Inhibitors of the epithelial sodium channel (ENaC) have therapeutic potential in CF airways to reduce hyperstimulated sodium and fluid absorption to levels that can restore airway hydration. OBJECTIVES: To determine whether a novel compound (QUB-TL1) designed to inhibit protease/ENaC signaling in CF airways restores ASL volume and mucociliary function...
September 15, 2016: American Journal of Respiratory and Critical Care Medicine
Benedict Wu, Joseph Capilato, Michelle P Pham, Jean Walker, Bernd Spur, Ana Rodriguez, Lark J Perez, Kingsley Yin
Bacterial infections can quickly turn into sepsis, with its attendant clinical sequelae of inflammation, tissue injury, and organ failure. Paradoxically, sustained inflammation in sepsis may lead to immune suppression, because of which the host is unable to clear the existing infection. Use of agents that suppress the inflammatory response may accelerate host immune suppression, whereas use of traditional antibiotics does not significantly affect inflammation. In this study, we investigated whether lipoxin A4 (LXA4), a specialized, proresolution lipid mediator, could increase neutrophil phagocytic activity as well as reduce bacterial virulence...
June 2016: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
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