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Bacterial exotoxin

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https://www.readbyqxmd.com/read/28632753/mait-cells-launch-a-rapid-robust-and-distinct-hyperinflammatory-response-to-bacterial-superantigens-and-quickly-acquire-an-anergic-phenotype-that-impedes-their-cognate-antimicrobial-function-defining-a-novel-mechanism-of-superantigen-induced-immunopathology
#1
Christopher R Shaler, Joshua Choi, Patrick T Rudak, Arash Memarnejadian, Peter A Szabo, Mauro E Tun-Abraham, Jamie Rossjohn, Alexandra J Corbett, James McCluskey, John K McCormick, Olivier Lantz, Roberto Hernandez-Alejandro, S M Mansour Haeryfar
Superantigens (SAgs) are potent exotoxins secreted by Staphylococcus aureus and Streptococcus pyogenes. They target a large fraction of T cell pools to set in motion a "cytokine storm" with severe and sometimes life-threatening consequences typically encountered in toxic shock syndrome (TSS). Given the rapidity with which TSS develops, designing timely and truly targeted therapies for this syndrome requires identification of key mediators of the cytokine storm's initial wave. Equally important, early host responses to SAgs can be accompanied or followed by a state of immunosuppression, which in turn jeopardizes the host's ability to combat and clear infections...
June 2017: PLoS Biology
https://www.readbyqxmd.com/read/28473665/anti-tumor-activity-of-an-immunotoxin-tgf%C3%AE-pe38-delivered-by-attenuated-salmonella-typhimurium
#2
Daejin Lim, Kwang Soo Kim, Hyunju Kim, Kyong-Cheol Ko, Jae Jun Song, Jong Hyun Choi, Minsang Shin, Jung-Joon Min, Jae-Ho Jeong, Hyon E Choy
The anticancer strategy underlying the use of immunotoxins is as follows: the cancer-binding domain delivers the toxin to a cancer cell, after which the toxin enters and kills the cell. TGFα-PE38 is an immunotoxin comprising transforming growth factor alpha (TGFα), a natural ligand of epidermal growth factor receptor (EGFR), and a modified Pseudomonas exotoxin A (PE38) lacking N terminal cell-binding domain, a highly potent cytotoxic protein moiety. Tumor cells with high level of EGFR undergo apoptosis upon treatment with TGFα-PE38...
June 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28453568/baicalin-inhibits-biofilm-formation-attenuates-the-quorum-sensing-controlled-virulence-and-enhances-pseudomonas-aeruginosa-clearance-in-a-mouse-peritoneal-implant-infection-model
#3
Jing Luo, Biying Dong, Ke Wang, Shuangqi Cai, Tangjuan Liu, Xiaojing Cheng, Danqing Lei, Yanling Chen, Yanan Li, Jinliang Kong, Yiqiang Chen
The quorum sensing (QS) circuit plays a role in the precise regulation of genes controlling virulence factors and biofilm formation in Pseudomonas aeruginosa. QS-controlled biofilm formation by Pseudomonas aeruginosa in clinical settings has remained controversial due to emerging drug resistance; therefore, screening diverse compounds for anti-biofilm or anti-QS activities is important. This study demonstrates the ability of sub-minimum inhibitory concentrations (sub-MICs) of baicalin, an active natural compound extracted from the traditional Chinese medicinal Scutellaria baicalensis, to inhibit the formation of Pseudomonas aeruginosa biofilms and enhance the bactericidal effects of various conventional antibiotics in vitro...
2017: PloS One
https://www.readbyqxmd.com/read/28427828/a-combined-clostridium-perfringens-trueperella-pyogenes-inactivated-vaccine-induces-complete-immunoprotection-in-a-mouse-model
#4
Wenlong Zhang, Pu Wang, Bing Wang, Bo Ma, Junwei Wang
Clostridium perfringens (C. perfringens) and Trueperella pyogenes (T. pyogenes) are two bacterial pathogens frequently associated with wound infections and following lethal complications in livestock. However, prudent use of antimicrobial agents is highly required given the emergence of multidrug-resistant strains of both bacteria and need for food safety. In the current study, a combined vaccine, composed of inactivated C. perfringens and T. pyogenes, was prepared. The amount of formaldehyde being used to inactivate two bacteria was optimized to retain the immunogenicity of antigens...
April 17, 2017: Biologicals: Journal of the International Association of Biological Standardization
https://www.readbyqxmd.com/read/28387795/antagonistic-interactions-of-soil-pseudomonads-are-structured-in-time
#5
Susanne A Kraemer, Jean-Paul R Soucy, Rees Kassen
Social interactions have been invoked as potential major selective forces structuring natural microbial communities and thus may help explain the astonishing bacterial diversity of natural ecosystems. Here, we investigate the prevalence and structure of exotoxin-mediated antagonistic interactions among free-living soil Pseudomonas strains collected over the course of two years at distances of up to one kilometer. Unlike some previous studies on antagonistic interactions among natural isolates, we found the prevalence of exotoxin-mediated inhibitions to be relatively low...
April 6, 2017: FEMS Microbiology Ecology
https://www.readbyqxmd.com/read/28348855/emergence-of-a-novel-lineage-containing-a-prophage-in-emm-m3-group-a-streptococcus-associated-with-upsurge-in-invasive-disease-in-the-uk
#6
Ali Al-Shahib, Anthony Underwood, Baharak Afshar, Claire E Turner, Theresa Lamagni, Shiranee Sriskandan, Androulla Efstratiou
A sudden increase in invasive Group A Streptococcus (iGAS) infections associated with emm/M3 isolates during the winter of 2008/09 prompted the initiation of enhanced surveillance in England. In order to characterise the population of emm/M3 GAS within the UK and determine bacterial factors that might be responsible for this upsurge, 442 emm/M3 isolates from cases of invasive and non-invasive infections during the period 2001-2013 were subjected to whole genome sequencing. MLST analysis differentiated emm/M3 isolates into three sequence types (STs): ST15, ST315 and ST406...
June 2016: Microbial Genomics
https://www.readbyqxmd.com/read/28282218/immunotoxins-in-cancer-therapy-review-and-update
#7
Bahman Akbari, Safar Farajnia, Shiva Ahdi Khosroshahi, Fatemeh Safari, Mohammadreza Yousefi, Hassan Dariushnejad, Leila Rahbarnia
Immunotoxins are a novel class of cancer therapeutics that contains a cytotoxic agent fused to a targeting moiety. Various toxic agents from different sources are used in immunotoxin development, including bacterial, plant and human origin cytotoxic elements. Although bacterial and plant-derived toxins are highly toxic and commonly used in immunotoxins, their immunogenicity for human restricted their application in cancer therapy. Here, we discuss the advantages and limitations of bacterial toxins such as Pseudomonas and Diphtheria toxins, plant toxins such as ricin and gelonin, and some endogenous protein of human origin such as RNases and Granzymes...
March 1, 2017: International Reviews of Immunology
https://www.readbyqxmd.com/read/28008818/deletion-of-a-putative-nlpc-p60-endopeptidase-bas1812-affects-germination-long-term-survival-and-endospore-formation-in-bacillus-anthracis
#8
Se Kye Kim, Yun Min Park, Kyoung Hwa Jung, Young Gyu Chai
Bacillus anthracis, an etiologic agent of the zoonotic disease anthrax, encodes a putative NlpC/P60 endopeptidase BAS1812. It harbors a signal peptide, three bacterial SH3 domains and an NlpC/P60 family domain. Previous studies showed that BAS1812 is immunogenic in infected hosts and is a potential biomarker for anthrax treatment. To date, however, little information is known about its function and involvement in anthrax pathogenesis. Here we describe the phenotypic effect of BAS1812 deletion in B. anthracis Sterne strain...
December 23, 2016: Microbiology
https://www.readbyqxmd.com/read/28003734/debs-a-unification-theory-for-dry-eye-and-blepharitis
#9
James M Rynerson, Henry D Perry
For many years, blepharitis and dry eye disease have been thought to be two distinct diseases, and evaporative dry eye distinct from aqueous insufficiency. In this treatise, we propose a new way of looking at dry eye, both evaporative and insufficiency, as the natural sequelae of decades of chronic blepharitis. Dry eye is simply the late form and late manifestation of one disease, blepharitis. We suggest the use of a new term in describing this one chronic disease, namely dry eye blepharitis syndrome (DEBS)...
2016: Clinical Ophthalmology
https://www.readbyqxmd.com/read/27965655/repression-of-rgg-but-not-upregulation-of-lacd-1-in-emm1-type-covs-mutant-mediates-the-speb-repression-in-group-a-streptococcus
#10
Chuan Chiang-Ni, Teng-Ping Chu, Jiunn-Jong Wu, Cheng-Hsun Chiu
CovR/CovS is an important two-component regulatory system in human pathogen group A Streptococcus (GAS). Epidemiological studies have shown that inactivation of the sensor kinase CovS is correlated with invasive clinical manifestations. The phosphorylation level of response regulator CovR decreases dramatically in the absence of CovS, resulting in the derepression of virulence factor expression and an increase in bacterial invasiveness. Streptococcal pyrogenic exotoxin B (SpeB) is a cysteine protease and is negatively regulated by CovR; however, the expression of SpeB is almost completely repressed in the covS mutant...
2016: Frontiers in Microbiology
https://www.readbyqxmd.com/read/27925510/passive-therapy-with-humanized-anti-staphylococcal-enterotoxin-b-antibodies-attenuates-systemic-inflammatory-response-and-protects-from-lethal-pneumonia-caused-by-staphylococcal-enterotoxin-b-producing-staphylococcus-aureus
#11
Melissa J Karau, Mulualem E Tilahun, Ashton Krogman, Barbara A Osborne, Richard A Goldsby, Chella S David, Jayawant N Mandrekar, Robin Patel, Govindarajan Rajagopalan
Drugs such as linezolid that inhibit bacterial protein synthesis may be beneficial in treating infections caused by toxigenic Staphylococcus aureus. As protein synthesis inhibitors have no effect on preformed toxins, neutralization of pathogenic exotoxins with anti-toxin antibodies may be beneficial in conjunction with antibacterial therapy. Herein, we evaluated the efficacy of human-mouse chimeric high-affinity neutralizing anti-staphylococcal enterotoxin B (SEB) antibodies in the treatment of experimental pneumonia caused by SEB-producing S...
December 7, 2016: Virulence
https://www.readbyqxmd.com/read/27915984/structure-function-and-evolution-of-clostridium-botulinum-c2-and-c3-toxins-insight-to-poultry-and-veterinary-vaccines
#12
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
https://www.readbyqxmd.com/read/27834892/towards-engineering-novel-pe-based-immunotoxins-by-targeting-them-to-the-nucleus
#13
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
https://www.readbyqxmd.com/read/27701380/identification-of-helicobacter-pylori-and-the-evolution-of-an-efficacious-childhood-vaccine-to-protect-against-gastritis-and-peptic-ulcer-disease
#14
REVIEW
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...
January 2017: Pediatric Research
https://www.readbyqxmd.com/read/27686742/bithionol-blocks-pathogenicity-of-bacterial-toxins-ricin-and-zika-virus
#15
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
https://www.readbyqxmd.com/read/27532004/editorial-bacterial-exotoxins-how-bacteria-fight-the-immune-system
#16
Inka Sastalla, Denise M Monack, Katharina F Kubatzky
No abstract text is available yet for this article.
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27498852/control-of-quorum-sensing-and-virulence-factors-of-pseudomonas-aeruginosa-using-phenylalanine-arginyl-%C3%AE-naphthylamide
#17
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
https://www.readbyqxmd.com/read/27469304/multivalent-inhibitors-of-channel-forming-bacterial-toxins
#18
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
https://www.readbyqxmd.com/read/27469199/utilizing-ayurvedic-literature-for-the-identification-of-novel-phytochemical-inhibitors-of-botulinum-neurotoxin-a
#19
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...
February 2, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/27463727/protection-of-the-furin-cleavage-site-in-low-toxicity-immunotoxins-based-on-pseudomonas-exotoxin-a
#20
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
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