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Bacterial exotoxin

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https://www.readbyqxmd.com/read/29031928/the-role-of-purified-clostridium-difficile-glucosylating-toxins-in-disease-pathogenesis-utilizing-a-murine-cecum-injection-model
#1
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
#2
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 a 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...
October 11, 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
#3
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
#4
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
#5
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...
September 18, 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
#6
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
#7
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
https://www.readbyqxmd.com/read/28758636/the-pseudomonas-aeruginosa-dnak-gene-is-involved-in-bacterial-translocation-across-the-intestinal-epithelial-cell-barrier
#8
Jun Okuda, Satoshi Yamane, Syouya Nagata, Chinami Kunikata, Chigusa Suezawa, Masashi Yasuda
Pseudomonas aeruginosa can penetrate through polarized epithelial cell monolayers produced by the human adenocarcinoma cell line Caco-2. We previously identified genes associated with bacterial translocation through Caco-2 cell monolayers by analysing transposon insertion mutants with dramatically reduced penetration activity relative to that of the wild-type P. aeruginosa PAO1 strain. In this study, we focused on the dnaK mutant because the association between this gene and penetration activity is unknown...
July 31, 2017: Microbiology
https://www.readbyqxmd.com/read/28724662/the-role-of-antibiotics-in-modulating-virulence-in-staphylococcus-aureus
#9
REVIEW
Elisabeth Hodille, Warren Rose, Binh An Diep, Sylvain Goutelle, Gerard Lina, Oana Dumitrescu
Staphylococcus aureus is often involved in severe infections, in which the effects of bacterial virulence factors have great importance. Antistaphylococcal regimens should take into account the different effects of antibacterial agents on the expression of virulence factors and on the host's immune response. A PubMed literature search was performed to select relevant articles on the effects of antibiotics on staphylococcal toxin production and on the host immune response. Information was sorted according to the methods used for data acquisition (bacterial strains, growth models, and antibiotic concentrations) and the assays used for readout generation...
October 2017: Clinical Microbiology Reviews
https://www.readbyqxmd.com/read/28648860/global-emergence-of-the-widespread-pseudomonas-aeruginosa-st235-clone
#10
Panisa Treepong, Veronica N Kos, Christophe Guyeux, Dominique S Blanc, Xavier Bertrand, Benoit Valot, Didier Hocquet
OBJECTIVES: Despite the non-clonal epidemic population structure of Pseudomonas aeruginosa, several multi-locus sequence types are distributed worldwide and are frequently associated with epidemics where multidrug resistance confounds treatment. ST235 is the most prevalent of these widespread clones. In this study we aimed to understand the origin of ST235 and the molecular basis for its success. METHODS: The genomes of 79 P. aeruginosa ST235 isolates collected worldwide over a 27-year period were examined...
June 22, 2017: Clinical Microbiology and Infection
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
#11
COMPARATIVE STUDY
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
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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...
July 4, 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
#18
Se Kye Kim, Yun Min Park, Kyoung Hwa Jung, Young Gyu Chai
Bacillus anthracis, an aetiologic agent of the zoonotic disease anthrax, encodes a putative NlpC/P60 endopeptidase BAS1812. It harbours 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...
February 2017: Microbiology
https://www.readbyqxmd.com/read/28003734/debs-a-unification-theory-for-dry-eye-and-blepharitis
#19
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
#20
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
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