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Bacterial exotoxin

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https://www.readbyqxmd.com/read/29438358/strategies-to-improve-the-clinical-utility-of-saporin-based-targeted-toxins
#1
REVIEW
Francesco Giansanti, David J Flavell, Francesco Angelucci, Maria Serena Fabbrini, Rodolfo Ippoliti
Plant Ribosome-inactivating proteins (RIPs) including the type I RIP Saporin have been used for the construction of Immunotoxins (ITxs) obtained via chemical conjugation of the toxic domain to whole antibodies or by generating genetic fusions to antibody fragments/targeting domains able to direct the chimeric toxin against a desired sub-population of cancer cells. The high enzymatic activity, stability and resistance to conjugation procedures and especially the possibility to express recombinant fusions in yeast, make Saporin a well-suited tool for anti-cancer therapy approaches...
February 13, 2018: Toxins
https://www.readbyqxmd.com/read/29421028/clostridial-abomasitis-and-enteritis-in-ruminants
#2
REVIEW
Katharine M Simpson, Robert J Callan, David C Van Metre
Clostridial abomasitis and enteritis are important alimentary diseases observed in all domestic ruminant species. These diseases most commonly result from overgrowth of Clostridium perfringens types A, B, C, D, and E with the associated release of bacterial exotoxins that result in necrosis of the abomasal or intestinal mucosa. Clostridium difficile may also be associated with enteritis in calves but is much less common than disease caused by C perfringens. This article reviews the causes, pathophysiology, clinical signs, diagnosis, treatment, and prevention of clostridial gastrointestinal diseases in ruminants...
March 2018: Veterinary Clinics of North America. Food Animal Practice
https://www.readbyqxmd.com/read/29412796/construction-and-recombinant-expression-of-pseudomonas-aeruginosa-truncated-exotoxin-a-in-escherichia-coli
#3
Hina Qaiser, Farheen Aslam, Saima Iftikhar, Adeen Farooq
Pseudomonas aeruginosa exotoxin A (PE) is a bacterial toxin composed of three domains namely: cell binding, translocation and enzymatic domain. The cytotoxic activity of PE is attributed to the enzymatic domain, which inhibits protein synthesis through ADP-ribosylation of EF-2. PE can be genetically modified to fight cancer. In this regard, a truncated and modified form of PE was produced that could be used for more potent immunotoxins. This modified form termed PE38KDEL was completely devoid of cell binding domain and parts of translocation domain II and Ib which are reported to be inessential for cytotoxicity of the toxin...
January 31, 2018: Cellular and Molecular Biology
https://www.readbyqxmd.com/read/29378883/the-endopeptidase-pepo-regulates-the-speb-cysteine-protease-and-is-essential-for-the-virulence-of-invasive-m1t1-streptococcus-pyogenes
#4
Stephan Brouwer, Amanda J Cork, Cheryl-Lynn Y Ong, Timothy C Barnett, Nicholas P West, Kevin S McIver, Mark J Walker
Streptococcus pyogenes (Group A Streptococcus, GAS) causes a wide range of human infections. The pathogenesis of GAS infections is dependent on the temporal expression of numerous secreted and surface-associated virulence factors that interact with host proteins. Streptococcal pyrogenic exotoxin B (SpeB) is one of the most extensively studied toxins produced by GAS, and the coordinate growth phase-dependent regulation of speB expression is linked to disease severity phenotypes. Here we identified the endopeptidase PepO as a novel growth phase-dependent regulator of SpeB in the invasive GAS M1-serotype strain 5448...
January 29, 2018: Journal of Bacteriology
https://www.readbyqxmd.com/read/29373309/metabolic-dependent-and-independent-ph-drop-shuts-down-virsr-quorum-sensing-in-clostridium-perfringens
#5
Keika Adachi, Kaori Ohtani, Michio Kawano, Ravindra Pal Singh, Basit Yousuf, Kenji Sonomoto, Tohru Shimizu, Jiro Nakayama
Clostridium perfringens produces various exotoxins and enzymes that cause food poisoning and gas gangrene. The genes involved in virulence are regulated by the agr-like quorum sensing (QS) system, which consists of a QS signal synthesis system and a VirSR two-component regulatory system (VirSR TCS) which is a global regulatory system composed of signal sensor kinase (VirS) and response regulator (VirR). We found that the perfringolysin O gene (pfoA) was transiently expressed during mid-log phase of bacterial growth; its expression was rapidly shut down thereafter, suggesting the existence of a self-quorum quenching (sQQ) system...
January 17, 2018: Journal of Bioscience and Bioengineering
https://www.readbyqxmd.com/read/29370247/broad-adsorption-of-sepsis-related-pamp-and-damp-molecules-mycotoxins-and-cytokines-from-whole-blood-using-cytosorb%C3%A2-sorbent-porous-polymer-beads
#6
Maryann C Gruda, Karl-Gustav Ruggeberg, Pamela O'Sullivan, Tamaz Guliashvili, Andrew R Scheirer, Thomas D Golobish, Vincent J Capponi, Phillip P Chan
OBJECTIVE: Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. In sepsis and septic shock, pathogen-associated molecular pattern molecules (PAMPS), such as bacterial exotoxins, cause direct cellular damage and/or trigger an immune response in the host often leading to excessive cytokine production, a maladaptive systemic inflammatory response syndrome response (SIRS), and tissue damage that releases DAMPs, such as activated complement and HMGB-1, into the bloodstream causing further organ injury...
2018: PloS One
https://www.readbyqxmd.com/read/29277757/in-vitro-evaluation-of-humanized-de-immunized-anti-psma-immunotoxins-for-the-treatment-of-prostate-cancer
#7
Marta Michalska, Susanne Schultze-Seemann, Irina Kuckuck, Philipp Wolf
BACKGROUND: We generated humanized/de-immunized immunotoxins targeting the prostate-specific membrane antigen (PSMA) and tested their cytotoxic activity against prostate cancer cells in vitro. MATERIALS AND METHODS: The humanized/de-immunized version of our murine anti-PSMA single-chain antibody fragment (scFv) D7, termed hD7-1(VL-VH), was ligated to the 40-kDa toxin domain of Pseudomonas aeruginosa exotoxin A (PE40), and to the deimmunized 24-kDa toxin domains PE24 or PE24mut...
January 2018: Anticancer Research
https://www.readbyqxmd.com/read/29210983/the-potential-pathogenic-contributions-of-endothelial-barrier-and-arterial-contractile-dysfunction-to-shock-due-to-b-anthracis-lethal-and-edema-toxins
#8
REVIEW
Dante A Suffredini, Xizhong Cui, Wanying Xu, Yan Li, Peter Q Eichacker
Shock with B. anthracis infection is particularly resistant to conventional cardiovascular support and its mortality rate appears higher than with more common bacterial pathogens. As opposed to many bacteria that lack exotoxins directly depressing hemodynamic function, lethal and edema toxin (LT and ET respectively) both cause shock and likely contribute to the high lethality rate with B. anthracis. Selective inhibition of the toxins is protective in infection models, and administration of either toxin alone in animals produces hypotension with accompanying organ injury and lethality...
December 6, 2017: Toxins
https://www.readbyqxmd.com/read/29203881/in-vivo-tropism-of-salmonella-typhi-toxin-to-cells-expressing-a-multiantennal-glycan-receptor
#9
Yi-An Yang, Sohyoung Lee, Jun Zhao, Andrew J Thompson, Ryan McBride, Buyankhishig Tsogtbaatar, James C Paulson, Ruth Nussinov, Lingquan Deng, Jeongmin Song
Typhoid fever is a life-threatening disease, but little is known about the molecular bases for its unique clinical presentation. Typhoid toxin, a unique virulence factor of Salmonella Typhi (the cause of typhoid fever), recapitulates in an animal model many symptoms of typhoid fever. Typhoid toxin binding to its glycan receptor Neu5Ac is central, but, due to the ubiquity of Neu5Ac, how typhoid toxin causes specific symptoms remains elusive. Here we show that typhoid toxin displays in vivo tropism to cells expressing multiantennal glycoprotein receptors, particularly on endothelial cells of arterioles in the brain and immune cells, which is in line with typhoid symptoms...
December 4, 2017: Nature Microbiology
https://www.readbyqxmd.com/read/29188305/synergistic-cytotoxicity-of-a-prostate-cancer-specific-immunotoxin-in-combination-with-the-bh3-mimetic-abt-737
#10
Theresa Noll, Susanne Schultze-Seemann, Irina Kuckuck, Marta Michalska, Philipp Wolf
In many tumors, including prostate cancer, anti-apoptotic members of the Bcl-2 family are overexpressed and cause cell death resistance, which is a typical hallmark of cancer. Different therapeutic approaches, therefore, aim to restore the death mechanisms for enhanced apoptosis. Our recombinant immunotoxin D7(VL-VH)-PE40 is composed of the scFv D7(VL-VH) against the prostate-specific membrane antigen (PSMA) on the surface of prostate cancer cells and of the cytotoxic domain of the bacterial toxin Pseudomonas Exotoxin A (PE40)...
November 29, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/29080422/development-of-a-rapid-immunochromatographic-assay-to-detect-contamination-of-raw-oysters-with-enteropathogenic-vibrio-parahaemolyticus
#11
Junko Sakata, Taro Yonekita, Kentaro Kawatsu
Thermostable direct hemolysin (TDH) and TDH-related hemolysin (TRH) are major virulence factors of enteropathogenic Vibrio parahaemolyticus. TDH and TRH are bacterial exotoxins, and their presence in culture medium serves as a specific marker for detecting this significant pathogen. Here, we developed and evaluated an immunochromatographic assay (TDH/TRH-ICA) to simultaneously or individually detect TDH and TRH. The TDH/TRH-ICA detected TDH in all broth cultures of 47 V. parahaemolyticus strains carrying tdh...
October 14, 2017: International Journal of Food Microbiology
https://www.readbyqxmd.com/read/29056305/exotoxins-and-endotoxins-inducers-of-inflammatory-cytokines
#12
REVIEW
Jean-Marc Cavaillon
Endotoxins and exotoxins are among the most potent bacterial inducers of cytokines. During infectious processes, the production of inflammatory cytokines including tumor necrosis factor (TNF), interleukin-1β (IL-1β), gamma interferon (IFNγ) and chemokines orchestrates the anti-infectious innate immune response. However, an overzealous production, leading up to a cytokine storm, can be deleterious and contributes to mortality consecutive to sepsis or toxic shock syndrome. Endotoxins of Gram-negative bacteria (lipopolysaccharide, LPS) are particularly inflammatory because they generate auto-amplificatory loops after activation of monocytes/macrophages...
October 19, 2017: Toxicon: Official Journal of the International Society on Toxinology
https://www.readbyqxmd.com/read/29051057/mannheimia-haemolytica-a2-secretes-different-proteases-into-the-culture-medium-and-in-outer-membrane-vesicles
#13
Gerardo Ramírez Rico, Moisés Martínez-Castillo, Cynthia González-Ruíz, Sarahí Luna-Castro, Mireya de la Garza
Respiratory diseases in ruminants have a significantly negative impact on the worldwide economy. The bacterium Mannheimia haemolytica is involved in pneumonic infections in bovine and ovine. In gram-negative bacteria, six secretion systems related to the colonization process and host tissue damage have been reported. In addition, in the last two decades, the production of outer membrane vesicles has been studied as a different bacterial strategy to release virulence factors, such as exotoxins, lipopolysaccharides, and proteases...
October 17, 2017: Microbial Pathogenesis
https://www.readbyqxmd.com/read/29031928/the-role-of-purified-clostridium-difficile-glucosylating-toxins-in-disease-pathogenesis-utilizing-a-murine-cecum-injection-model
#14
Yongrong Zhang, Zhiyong Yang, Si Gao, Therwa Hamza, Harris G Yfantis, Michael Lipsky, Hanping Feng
Most pathogenic Clostridium difficile produce two major exotoxins TcdA and TcdB, in the absence of which the bacterium is non-pathogenic. While it is important to investigate the role of each toxin in the pathogenesis of C. difficile infection (CDI) using isogenic strains, it is impossible to precisely control the expression levels of individual toxins and exclude bacterial factors that may contribute to the toxins' effects during infection. In this study, we utilized an acute intestinal disease model by injecting purified toxins directly into mouse cecum after a midline laparotomy...
October 12, 2017: Anaerobe
https://www.readbyqxmd.com/read/29019389/intracellular-protein-delivery-system-using-a-target-specific-repebody-and-translocation-domain-of-bacterial-exotoxin
#15
Hee-Yeon Kim, Jung Ae Kang, Jeong-Hyun Ryou, Gyeong Hee Lee, Dae Seong Choi, Dong Eun Lee, Hak-Sung Kim
With the high efficacy of protein-based therapeutics and plenty of intracellular drug targets, cytosolic protein delivery in a cell-specific manner has attracted considerable attention in the field of precision medicine. Herein, we present an intracellular protein delivery system based on a target-specific repebody and the translocation domain of Pseudomonas aeruginosa exotoxin A. The delivery platform was constructed by genetically fusing an EGFR-specific repebody as a targeting moiety to the translocation domain, while a protein cargo was fused to the C-terminal end of the delivery platform...
November 17, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28939555/a-novel-therapeutic-strategy-for-pancreatic-cancer-targeting-cell-surface-glycan-using-rbc2lc-n-lectin-drug-conjugate-ldc
#16
Osamu Shimomura, Tatsuya Oda, Hiroaki Tateno, Yusuke Ozawa, Sota Kimura, Shingo Sakashita, Masayuki Noguchi, Jun Hirabayashi, Makoto Asashima, Nobuhiro Ohkohchi
Various cancers, including pancreatic ductal adenocarcinoma (PDAC), remain intractable even with costly tumour-targeting antibody drugs. Because the outermost coatings of cancer cells are composed of cell-specific glycan layers (glycocalyx), lectins, proteins with glycan-binding potential, were evaluated for possible use as drug carriers in PDAC treatment. A human PDAC cell line with well-to-moderately differentiated properties (Capan-1) was subjected to lectin microarray analysis to identify specific lectin-glycan pairs...
September 22, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28928212/population-and-whole-genome-sequence-based-characterization-of-invasive-group-a-streptococci-recovered-in-the-united-states-during-2015
#17
Sopio Chochua, Ben J Metcalf, Zhongya Li, Joy Rivers, Saundra Mathis, Delois Jackson, Robert E Gertz, Velusamy Srinivasan, Ruth Lynfield, Chris Van Beneden, Lesley McGee, Bernard Beall
Group A streptococci (GAS) are genetically diverse. Determination of strain features can reveal associations with disease and resistance and assist in vaccine formulation. We employed whole-genome sequence (WGS)-based characterization of 1,454 invasive GAS isolates recovered in 2015 by Active Bacterial Core Surveillance and performed conventional antimicrobial susceptibility testing. Predictions were made for genotype, GAS carbohydrate, antimicrobial resistance, surface proteins (M family, fibronectin binding, T, R28), secreted virulence proteins (Sda1, Sic, exotoxins), hyaluronate capsule, and an upregulated nga operon (encodes NADase and streptolysin O) promoter (Pnga3)...
September 19, 2017: MBio
https://www.readbyqxmd.com/read/28923955/leaderless-secreted-peptide-signaling-molecule-alters-global-gene-expression-and-increases-virulence-of-a-human-bacterial-pathogen
#18
Hackwon Do, Nishanth Makthal, Arica R VanderWal, Mandy Rettel, Mikhail M Savitski, Nikolai Peschek, Kai Papenfort, Randall J Olsen, James M Musser, Muthiah Kumaraswami
Successful pathogens use complex signaling mechanisms to monitor their environment and reprogram global gene expression during specific stages of infection. Group A Streptococcus (GAS) is a major human pathogen that causes significant disease burden worldwide. A secreted cysteine protease known as streptococcal pyrogenic exotoxin B (SpeB) is a key virulence factor that is produced abundantly during infection and is critical for GAS pathogenesis. Although identified nearly a century ago, the molecular basis for growth phase control of speB gene expression remains unknown...
October 3, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28851366/a-widespread-family-of-polymorphic-toxins-encoded-by-temperate-phages
#19
Anne Jamet, Marie Touchon, Bruno Ribeiro-Gonçalves, João André Carriço, Alain Charbit, Xavier Nassif, Mario Ramirez, Eduardo P C Rocha
BACKGROUND: Polymorphic toxins (PTs) are multi-domain bacterial exotoxins belonging to distinct families that share common features in terms of domain organization. PTs are found in all major bacterial clades, including many toxic effectors of type V and type VI secretion systems. PTs modulate the dynamics of microbial communities by killing or inhibiting the growth of bacterial competitors lacking protective immunity proteins. RESULTS: In this work, we identified a novel widespread family of PTs, named MuF toxins, which were exclusively encoded within temperate phages and their prophages...
August 29, 2017: BMC Biology
https://www.readbyqxmd.com/read/28822159/-effect-of-sodium-houttuyfonate-in-combination-with-erythromycin-on-luxs-agr-rna%C3%A2-of-staphylococus-epidermidis
#20
Gan-Fei Xu, Jing-Jing Wang, Da-Qiang Wu, Yan Guan
Quorum sensing of bacteria and its specific gene expression regulation have a very important role in bacterial biofilm formation. LuxS and agr are the key regulatory genes in quorum sensing of Staphylococcus epidermidis, and RNA Ⅲ is the effector molecule of agr system. In order to evaluate the effects of sodium houttuyfonate in combination with erythromycin on the transcription level of S. epidermidis, serial dilution method was used to determine the MIC of sodium houttuyfonate, erythromycin and vancomycin on S...
June 2017: Zhongguo Zhong Yao za Zhi, Zhongguo Zhongyao Zazhi, China Journal of Chinese Materia Medica
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