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Bacterial toxin

Vera Pader, Sanika Hakim, Kimberley L Painter, Sivaramesh Wigneshweraraj, Thomas B Clarke, Andrew M Edwards
Daptomycin is a bactericidal antibiotic of last resort for serious infections caused by methicillin-resistant Staphylococcus aureus (MRSA)(1,2). Although resistance is rare, treatment failure can occur in more than 20% of cases(3,4) and so there is a pressing need to identify and mitigate factors that contribute to poor therapeutic outcomes. Here, we show that loss of the Agr quorum-sensing system, which frequently occurs in clinical isolates, enhances S. aureus survival during daptomycin treatment. Wild-type S...
October 24, 2016: Nature Microbiology
Petra Břehová, Markéta Šmídková, Jan Skácel, Martin Dračínský, Helena Mertlíková-Kaiserová, Monica P Soto Velasquez, Val J Watts, Zlatko Janeba
Bordetella pertussis adenylate cyclase toxin (ACT) and Bacillus anthracis edema factor (EF) are key virulence factors with adenylate cyclase (AC) activity that substantially contribute to the pathogenesis of whooping cough and anthrax, respectively. There is an urgent need to develop potent and selective inhibitors of bacterial ACs with prospects for the development of potential antibacterial therapeutics and to study their molecular interactions with the target enzymes. Novel fluorescent 5-chloroanthraniloyl-substituted acyclic nucleoside phosphonates (Cl-ANT-ANPs) were designed and synthesized in the form of their diphosphates (Cl-ANT-ANPpp) as competitive ACT and EF inhibitors with sub-micromolar potency (IC50 values: 11-622 nm)...
October 24, 2016: ChemMedChem
Viviana Guadagni, Chiara Cerri, Ilaria Piano, Elena Novelli, Claudia Gargini, Carla Fiorentini, Matteo Caleo, Enrica Strettoi
Retinitis pigmentosa (RP) comprises a group of inherited pathologies characterized by progressive photoreceptor degeneration. In rodent models of RP, expression of defective genes and retinal degeneration usually manifest during the first weeks of postnatal life, making it difficult to distinguish consequences of primary genetic defects from abnormalities in retinal development. Moreover, mouse eyes are small and not always adequate to test pharmacological and surgical treatments. An inducible paradigm of retinal degeneration potentially extensible to large animals is therefore desirable...
October 24, 2016: Scientific Reports
Javier Sanchez-Villamil, Gabriela Tapia-Pastrana, Fernando Navarro-Garcia
Inflammatory response is key for the host defense against diarrheagenic Escherichia coli and contributes to the pathogenesis of the disease but there is not a comparative study among different diarrheagenic pathotypes. We analyzed the inflammatory response induced by five diarrheagenic pathotypes in a HT-29 cell infection model. The model was unified to reproduce the pathogenesis of each pathotype. To compare the inflammatory responses we evaluated: (i) nuclear NF-κB and ERK1/2 translocation by confocal microscopy; (ii) kinetics of activation by each pathway detecting p65 and ERK1/2 phosphorylation by Western blotting; (iii) pathways modulation through bacterial infections with or without co-stimulation with TNF-α or EGF; (iv) cytokine profile induced by each pathotype with and without inhibitors of each pathway...
2016: Frontiers in Cellular and Infection Microbiology
Andrea Du Toit
No abstract text is available yet for this article.
October 24, 2016: Nature Reviews. Microbiology
G Kamkamidze, I Migriauli, D Razmadze, M Kochlamazashvili, K Mulkijanyan, M Butsashvili
The main objective of this investigation was to develop and pilot a real-time Polymerase Chain Reaction (rt-PCR) diagnostic system for rapid and simultaneous identification of pathogens with a particular emphasis on diarrheal disease diagnostics. The diarrheal diseases were selected as a target for the pilot because they constitute a primary public health priority in Georgia and worldwide. The product developed by our research team "Neo_PCR_Diagnostics" represents an original system for the identification of pathogens associated with gastrointestinal tract infections and diarrhea...
September 2016: Georgian Medical News
Bartosz Roszniowski, Agnieszka Latka, Barbara Maciejewska, Dieter Vandenheuvel, Tomasz Olszak, Yves Briers, Giles S Holt, Miguel A Valvano, Rob Lavigne, Darren L Smith, Zuzanna Drulis-Kawa
Burkholderia phage AP3 (vB_BceM_AP3) is a temperate virus of the Myoviridae and the Peduovirinae subfamily (P2likevirus genus). This phage specifically infects multidrug-resistant clinical Burkholderia cenocepacia lineage IIIA strains commonly isolated from cystic fibrosis patients. AP3 exhibits high pairwise nucleotide identity (61.7 %) to Burkholderia phage KS5, specific to the same B. cenocepacia host, and has 46.7-49.5 % identity to phages infecting other species of Burkholderia. The lysis cassette of these related phages has a similar organization (putative antiholin, putative holin, endolysin, and spanins) and shows 29-98 % homology between specific lysis genes, in contrast to Enterobacteria phage P2, the hallmark phage of this genus...
October 21, 2016: Applied Microbiology and Biotechnology
Carsten Deppermann, Paul Kubes
The primary function of platelets is to patrol the vasculature and seal vessel breaches to limit blood loss. However, it is becoming increasingly clear that they also contribute to pathophysiological conditions like thrombosis, atherosclerosis, stroke and infection. Severe sepsis is a devastating disease that claims hundreds of thousands of lives every year in North America and is a major burden to the public health system. Platelet surface receptors like GPIb, αIIbβ3, TLR2 and TLR4 are involved in direct platelet-bacteria interactions...
October 18, 2016: Seminars in Immunology
Visweshwar Regode, Sreeramulu Kuruba, Akbar S Mohammad, Hari C Sharma
Bacillus thuringiensis toxin proteins are deployed in transgenic plants for pest management. The present studies were aimed at characterization of gut bacterial proteases involved in activation of inactive Cry1Ac protoxin (pro-Cry1Ac) to active toxin in Helicoverpa armigera. Bacterial strains were isolated from H. armigera midgut and screened for their proteolytic activation toward pro-Cry1Ac. Among 12 gut bacterial isolates seven isolates showed proteolytic activity, and proteases from three isolates (IVS1, IVS2, and IVS3) were found to be involved in the proteolytic conversion of pro-Cry1Ac into active toxin...
2016: Frontiers in Microbiology
Julia I Tandberg, Leidy X Lagos, Petter Langlete, Eva Berger, Anne-Lise Rishovd, Norbert Roos, Deepa Varkey, Ian T Paulsen, Hanne C Winther-Larsen
Membrane vesicles (MVs) are spherical particles naturally released from the membrane of Gram-negative bacteria. Bacterial MV production is associated with a range of phenotypes including biofilm formation, horizontal gene transfer, toxin delivery, modulation of host immune responses and virulence. This study reports comparative profiling of MVs from bacterial strains isolated from three widely disperse geographical areas. Mass spectrometry identified 119, 159 and 142 proteins in MVs from three different strains of Piscirickettsia salmonis isolated from salmonids in Chile (LF-89), Norway (NVI 5692) and Canada (NVI 5892), respectively...
2016: PloS One
Alexander E Lang, Sonja Kühn, Hans Georg Mannherz
Actin is one of the most abundant cellular proteins and an essential constituent of the actin cytoskeleton, which by its dynamic behavior participates in many cellular activities. The organization of the actin cytoskeleton is regulated by a large number of proteins and represents one of the major targets of bacterial toxins. A number of bacterial effector proteins directly modify actin: Clostridial bacteria produce toxins, which ADP-ribosylate actin at Arg177 leading to inhibition of actin polymerization. The bacterium Photorhabdus luminescens produces several types of protein toxins, including the high molecular weight Tc toxin complex, whose component TccC3 ADP-ribosylates actin at Thr148 promoting polymerization and aggregation of intracellular F-actin leading to inhibition of several cellular functions, such as phagocytosis...
October 19, 2016: Current Topics in Microbiology and Immunology
Mária Džunková, Giuseppe D'Auria, Hua Xu, Jun Huang, Yinghua Duan, Andrés Moya, Ciarán P Kelly, Xinhua Chen
Antibiotics have significant and long-lasting impacts on the intestinal microbiota and consequently reduce colonization resistance against Clostridium difficile infection (CDI). Standard therapy using antibiotics is associated with a high rate of disease recurrence, highlighting the need for novel treatment strategies that target toxins, the major virulence factors, rather than the organism itself. Human monoclonal antibodies MK-3415A (actoxumab-bezlotoxumab) to C. difficile toxin A and toxin B, as an emerging non-antibiotic approach, significantly reduced the recurrence of CDI in animal models and human clinical trials...
2016: Frontiers in Cellular and Infection Microbiology
Carla Pereira, Catarina Moreirinha, Magdalena Lewicka, Paulo Almeida, Carla Clemente, Jesús L Romalde, Maria L Nunes, Adelaide Almeida
In the present study two new phages (phT4A and ECA2) were characterized and their efficacy was evaluated separately and in cocktail (phT4A/ECA2) to control Escherichia coli. The isolated phages, phT4A and ECA2, belonged to the Myoviridae and Podoviridae family, respectively and both are safe (no integrase and toxin codifying genes) to be used in bacterial control. In general, the increase of multiplicity of infection (MOI) from 1 to 100 promoted a significant increase in the efficiency of phage phT4A and phage cocktail phT4A/ECA2...
October 15, 2016: Virus Research
Laura Julia Starost, Sascha Karassek, Yasuteru Sano, Takashi Kanda, Kwang Sik Kim, Ulrich Dobrindt, Christian Rüter, Marcus Alexander Schmidt
Pertussis toxin (PTx), the major virulence factor of the whooping cough-causing bacterial pathogen Bordetella pertussis, permeabilizes the blood-brain barrier (BBB) in vitro and in vivo. Breaking barriers might promote translocation of meningitis-causing bacteria across the BBB, thereby facilitating infection. PTx activates several host cell signaling pathways exploited by the neonatal meningitis-causing Escherichia coli K1-RS218 for invasion and translocation across the BBB. Here, we investigated whether PTx and E...
October 13, 2016: Toxins
Y Sun, L M Willis, H R Batchelder, M Nitz
Using a MALDI-MS based assay, the kinetic parameters for peptide glucosylation using the C. difficile toxin B glycosyltransferase domain were determined. The minimum consensus sequence for glucosylation was YXXTXFXXY and the optimal peptide found was YAPTVFDAY. Using this sequence, homogenous glucosylated proteins could be readily produced.
October 17, 2016: Chemical Communications: Chem Comm
Kerrie L May, Thomas J Silhavy
The outer membrane (OM) of Gram-negative bacteria is positioned at the frontline of the cell's interaction with its environment and provides a barrier against influx of external toxins while still allowing import of nutrients and excretion of wastes. It is a remarkable asymmetric bilayer with a glycolipid surface-exposed leaflet and a glycerophospholipid inner leaflet. Lipid asymmetry is key to OM barrier function and several different systems actively maintain this lipid asymmetry. All OM components are synthesized in the cytosol before being secreted and assembled into a contiguous membrane on the other side of the cell wall...
October 11, 2016: Biochimica et Biophysica Acta
Michele Chu, Michael J G Mallozzi, Bryan P Roxas, Lisa Bertolo, Mario A Monteiro, Al Agellon, V K Viswanathan, Gayatri Vedantam
Clostridium difficile is a diarrheagenic pathogen associated with significant mortality and morbidity. While its glucosylating toxins are primary virulence determinants, there is increasing appreciation of important roles for non-toxin factors in C. difficile pathogenesis. Cell wall glycopolymers (CWGs) influence the virulence of various pathogens. Five C. difficile CWGs, including PSII, have been structurally characterized, but their biosynthesis and significance in C. difficile infection is unknown. We explored the contribution of a conserved CWG locus to C...
October 2016: PLoS Pathogens
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
Taylor S Cohen, Omari Jones-Nelson, Meghan Hotz, Lily Cheng, Lloyd S Miller, JoAnn Suzich, C Kendall Stover, Bret R Sellman
Bacterial pneumonia, such as those caused by Staphylococcus aureus, is associated with an influx of inflammatory neutrophils into the lung tissue and airways. Regulation and clearance of recruited neutrophils is essential for preventing tissue damage by "friendly fire", a responsibility of macrophages in a process called efferocytosis. We hypothesized that S. aureus impairs efferocytosis by alveolar macrophages (AMs) through the activity of the secreted virulence factor alpha toxin (AT), which has been implicated in altering the antimicrobial function of AMs...
October 14, 2016: Scientific Reports
Julien Karim Malet, Pascale Cossart, David Ribet
Bacterial pathogens can interfere during infection with host cell organelles, such as mitochondria, the endoplasmic reticulum-Golgi system or nuclei. As important cellular functions are often compartmentalized in these organelles, their targeting allows pathogens to manipulate key host functions during infection. Here, we identify lysosomes as a new class of organelles targeted by the pathogenic bacterium Listeria monocytogenes. We demonstrate that extracellular Listeria, via secretion of the pore-forming toxin Listeriolysin O (LLO), alter lysosomal integrity in epithelial cells, but not in macrophages...
October 14, 2016: Cellular Microbiology
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