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The Role of Streptococcal and Staphylococcal Exotoxins and Proteases in Human Necrotizing Soft Tissue Infections
toxins Review The Role of Streptococcal and Staphylococcal Exotoxins and Proteases in Human Necrotizing Soft Tissue Infections Patience Shumba 1, Srikanth Mairpady Shambat 2 and Nikolai Siemens 1,* 1 Center for Functional Genomics of Microbes, Department of Molecular Genetics and Infection Biology, University of Greifswald, D-17489 Greifswald, Germany; [email protected] 2 Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich, CH-8091 Zurich, Switzerland; [email protected] * Correspondence: [email protected]; Tel.: +49-3834-420-5711 Received: 20 May 2019; Accepted: 10 June 2019; Published: 11 June 2019 Abstract: Necrotizing soft tissue infections (NSTIs) are critical clinical conditions characterized by extensive necrosis of any layer of the soft tissue and systemic toxicity. Group A streptococci (GAS) and Staphylococcus aureus are two major pathogens associated with monomicrobial NSTIs. In the tissue environment, both Gram-positive bacteria secrete a variety of molecules, including pore-forming exotoxins, superantigens, and proteases with cytolytic and immunomodulatory functions. The present review summarizes the current knowledge about streptococcal and staphylococcal toxins in NSTIs with a special focus on their contribution to disease progression, tissue pathology, and immune evasion strategies. Keywords: Streptococcus pyogenes; group A streptococcus; Staphylococcus aureus; skin infections; necrotizing soft tissue infections; pore-forming toxins; superantigens; immunomodulatory proteases; immune responses Key Contribution: Group A streptococcal and Staphylococcus aureus toxins manipulate host physiological and immunological responses to promote disease severity and progression. 1. Introduction Necrotizing soft tissue infections (NSTIs) are rare and represent a more severe rapidly progressing form of soft tissue infections that account for significant morbidity and mortality [1]. -
Assessing Neurotoxicity of Drugs of Abuse
National Institute on Drug Abuse RESEARCH MONOGRAPH SERIES Assessing Neurotoxicity of Drugs of Abuse 136 U.S. Department of Health and Human Services • Public Health Service • National Institutes of Health Assessing Neurotoxicity of Drugs of Abuse Editor: Lynda Erinoff, Ph.D. NIDA Research Monograph 136 1993 U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES Public Health Service National Institutes of Health National Institute on Drug Abuse 5600 Fishers Lane Rockville, MD 20857 ACKNOWLEDGMENT This monograph is based on the papers and discussions from a technical review on “Assessing Neurotoxicity of Drugs of Abuse” held on May 20-21, 1991, in Bethesda, MD. The technical review was sponsored by the National Institute on Drug Abuse (NIDA). COPYRIGHT STATUS NIDA has obtained permission from the copyright holders to reproduce certain previously published material as noted in the text. Further reproduction of this copyrighted material is permitted only as part of a reprinting of the entire publication or chapter. For any other use, the copyright holder’s permission is required. All other material in this volume except quoted passages from copyrighted sources is in the public domain and may be used or reproduced without permission from the Institute or the authors. Citation of the source is appreciated. Opinions expressed in this volume are those of the authors and do not necessarily reflect the opinions or official policy of the National Institute on Drug Abuse or any other part of the U.S. Department of Health and Human Services. The U.S. Government does not endorse or favor any specific commercial product or company. -
Penetration of Stratified Mucosa Cytolysins Augment Superantigen
Cytolysins Augment Superantigen Penetration of Stratified Mucosa Amanda J. Brosnahan, Mary J. Mantz, Christopher A. Squier, Marnie L. Peterson and Patrick M. Schlievert This information is current as of September 25, 2021. J Immunol 2009; 182:2364-2373; ; doi: 10.4049/jimmunol.0803283 http://www.jimmunol.org/content/182/4/2364 Downloaded from References This article cites 76 articles, 24 of which you can access for free at: http://www.jimmunol.org/content/182/4/2364.full#ref-list-1 Why The JI? Submit online. http://www.jimmunol.org/ • Rapid Reviews! 30 days* from submission to initial decision • No Triage! Every submission reviewed by practicing scientists • Fast Publication! 4 weeks from acceptance to publication *average by guest on September 25, 2021 Subscription Information about subscribing to The Journal of Immunology is online at: http://jimmunol.org/subscription Permissions Submit copyright permission requests at: http://www.aai.org/About/Publications/JI/copyright.html Email Alerts Receive free email-alerts when new articles cite this article. Sign up at: http://jimmunol.org/alerts The Journal of Immunology is published twice each month by The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 Copyright © 2009 by The American Association of Immunologists, Inc. All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. The Journal of Immunology Cytolysins Augment Superantigen Penetration of Stratified Mucosa1 Amanda J. Brosnahan,* Mary J. Mantz,† Christopher A. Squier,† Marnie L. Peterson,‡ and Patrick M. Schlievert2* Staphylococcus aureus and Streptococcus pyogenes colonize mucosal surfaces of the human body to cause disease. A group of virulence factors known as superantigens are produced by both of these organisms that allows them to cause serious diseases from the vaginal (staphylococci) or oral mucosa (streptococci) of the body. -
Biosafety Manual 2017
Biosafety Manual 2017 Revised 6/2017 Policy Statement It is the policy of Northern Arizona University (NAU) to provide a safe working environment. The primary responsibility for insuring safe conduct and conditions in the laboratory resides with the principal investigator. The Office of Biological Safety is committed to providing up-to-date information, training, and monitoring to the research and biomedical community concerning the safe conduct of biological, recombinant, and acute toxin research and the handling of biological materials in accordance with all pertinent local, state and federal regulations, guidelines, and laws. To that end, this manual is a resource, to be used in conjunction with the CDC and NIH guidelines, the NAU Select Agent Program, Biosafety in Microbiological and Biomedical Laboratories (BMBL), and other resource materials. Introduction This Biological Safety Manual is intended for use as a guidance document for researchers and clinicians who work with biological materials. It should be used in conjunction with the Laboratory-Specific Safety Manual, which provides more general safety information. These manuals describe policies and procedures that are required for the safe conduct of research at NAU. The NAU Personnel Policy on Safety 5.03 also provides guidance for safety in the workplace. Responsibilities In the academic research/teaching setting, the principal investigator (PI) is responsible for ensuring that all members of the laboratory are familiar with safe research practices. In the clinical laboratory setting, the faculty member who supervises the laboratory is responsible for safety practices. Lab managers, supervisors, technicians and others who provide supervisory roles in laboratories and clinical settings are responsible for overseeing the safety practices in laboratories and reporting any problems, accidents, and spills to the appropriate faculty member. -
Response of Cellular Innate Immunity to Cnidarian Pore-Forming Toxins
Review Response of Cellular Innate Immunity to Cnidarian Pore-Forming Toxins Wei Yuen Yap 1 and Jung Shan Hwang 2,* 1 Department of Biological Sciences, School of Science and Technology, Sunway University, No. 5 Jalan Universiti, Bandar Sunway, Selangor Darul Ehsan 47500, Malaysia; [email protected] 2 Department of Medical Sciences, School of Healthcare and Medical Sciences, Sunway University, No. 5 Jalan Universiti, Bandar Sunway, Selangor Darul Ehsan 47500, Malaysia * Correspondence: [email protected]; Tel.: +603-7491-8622 (ext. 7414) Academic Editor: Jean-Marc Sabatier Received: 23 August 2018; Accepted: 28 September 2018; Published: 4 October 2018 Abstract: A group of stable, water-soluble and membrane-bound proteins constitute the pore forming toxins (PFTs) in cnidarians. They interact with membranes to physically alter the membrane structure and permeability, resulting in the formation of pores. These lesions on the plasma membrane causes an imbalance of cellular ionic gradients, resulting in swelling of the cell and eventually its rupture. Of all cnidarian PFTs, actinoporins are by far the best studied subgroup with established knowledge of their molecular structure and their mode of pore-forming action. However, the current view of necrotic action by actinoporins may not be the only mechanism that induces cell death since there is increasing evidence showing that pore-forming toxins can induce either necrosis or apoptosis in a cell-type, receptor and dose-dependent manner. In this review, we focus on the response of the cellular immune system to the cnidarian pore-forming toxins and the signaling pathways that might be involved in these cellular responses. -
A Novel Superantigen Isolated from Pathogenic Strains of Streptococcus Pyogenes with Aminoterminal Homology to Staphylococcal Enterotoxins B and C
A novel superantigen isolated from pathogenic strains of Streptococcus pyogenes with aminoterminal homology to staphylococcal enterotoxins B and C. J A Mollick, … , D Grossman, R R Rich J Clin Invest. 1993;92(2):710-719. https://doi.org/10.1172/JCI116641. Research Article Streptococcus pyogenes (group A Streptococcus) has re-emerged in recent years as a cause of severe human disease. Because extracellular products are involved in streptococcal pathogenesis, we explored the possibility that a disease isolate expresses an uncharacterized superantigen. We screened culture supernatants for superantigen activity with a major histocompatibility complex class II-dependent T cell proliferation assay. Initial fractionation with red dye A chromatography indicated production of a class II-dependent T cell mitogen by a toxic shock-like syndrome (TSLS) strain. The amino terminus of the purified streptococcal superantigen was more homologous to the amino termini of staphylococcal enterotoxins B, C1, and C3 (SEB, SEC1, and SEC3), than to those of pyrogenic exotoxins A, B, C or other streptococcal toxins. The molecule, designated SSA, had the same pattern of class II isotype usage as SEB in T cell proliferation assays. However, it differed in its pattern of human T cell activation, as measured by quantitative polymerase chain reaction with V beta-specific primers. SSA activated human T cells that express V beta 1, 3, 15 with a minor increase of V beta 5.2-bearing cells, whereas SEB activated V beta 3, 12, 15, and 17-bearing T cells. Immunoblot analysis of 75 disease isolates from several localities detected SSA production only in group A streptococci, and found that SSA is apparently confined to only three clonal […] Find the latest version: https://jci.me/116641/pdf A Novel Superantigen Isolated from Pathogenic Strains of Streptococcus pyogenes with Aminoterminal Homology to Staphylococcal Enterotoxins B and C Joseph A. -
Retrograde Transport of Mutant Ricin to the Endoplasmic Reticulum with Subsequent Translocation to Cytosol (Ricin͞toxin͞translocation͞retrograde Transport͞sulfation)
Proc. Natl. Acad. Sci. USA Vol. 94, pp. 3783–3788, April 1997 Cell Biology Retrograde transport of mutant ricin to the endoplasmic reticulum with subsequent translocation to cytosol (ricinytoxinytranslocationyretrograde transportysulfation) ANDRZEJ RAPAK,PÅL Ø. FALNES, AND SJUR OLSNES* Institute for Cancer Research, The Norwegian Radium Hospital, Montebello, 0310 Oslo, Norway Communicated by R. John Collier, Harvard Medical School, Boston, MA, January 30, 1997 (received for review November 25, 1996) ABSTRACT Translocation of ricin A chain to the cytosol (20). Because this labeling takes place in the Golgi apparatus, only has been proposed to take place from the endoplasmic reticulum molecules that have already been transported retrograde to the (ER), but attempts to visualize ricin in this organelle have failed. Golgi complex will be labeled. Furthermore, because only the A Here we modified ricin A chain to contain a tyrosine sulfation chain carrying the sulfation site will be labeled, the B chain, which site alone or in combination with N-glycosylation sites. When migrates at almost the same rate as the modified A chain, will not reconstituted with ricin B chain and incubated with cells in the complicate the interpretation of the data. We here present 35 presence of Na2 SO4, the modified A chains were labeled. The evidence that sulfated ricin A chain is transported retrograde to labeling was prevented by brefeldin A and ilimaquinone, and it the ER and then translocated to the cytosol. appears to take place in the Golgi apparatus. This method allows selective labeling of ricin molecules that have already been MATERIALS AND METHODS 35 transported retrograde to this organelle. -
Functional Classification of Protein Toxins As a Basis for Bioinformatic
www.nature.com/scientificreports OPEN Functional classifcation of protein toxins as a basis for bioinformatic screening Received: 27 July 2017 Surendra S. Negi1, Catherine H. Schein1,2, Gregory S. Ladics3, Henry Mirsky4, Peter Chang4, Accepted: 2 October 2017 Jean-Baptiste Rascle5, John Kough6, Lieven Sterck 7, Sabitha Papineni8, Joseph M. Jez9, Published: xx xx xxxx Lucilia Pereira Mouriès10 & Werner Braun1 Proteins are fundamental to life and exhibit a wide diversity of activities, some of which are toxic. Therefore, assessing whether a specifc protein is safe for consumption in foods and feeds is critical. Simple BLAST searches may reveal homology to a known toxin, when in fact the protein may pose no real danger. Another challenge to answer this question is the lack of curated databases with a representative set of experimentally validated toxins. Here we have systematically analyzed over 10,000 manually curated toxin sequences using sequence clustering, network analysis, and protein domain classifcation. We also developed a functional sequence signature method to distinguish toxic from non-toxic proteins. The current database, combined with motif analysis, can be used by researchers and regulators in a hazard screening capacity to assess the potential of a protein to be toxic at early stages of development. Identifying key signatures of toxicity can also aid in redesigning proteins, so as to maintain their desirable functions while reducing the risk of potential health hazards. Most genetically engineered (GE) food crops involve expressing an introduced protein, thus assessing the safety of the protein is required before commercialization1–4. GE crops are created by introducing gene(s) from one species into a crop plant species to improve the nutritional value, yield, drought resistance, herbicide tolerance or pest resistance. -
Effect of Streptolysin O on Erythrocyte Membranes, Liposomes, and Lipid Dispersions
EFFECT OF STREPTOLYSIN O ON ERYTHROCYTE MEMBRANES, LIPOSOMES, AND LIPID DISPERSIONS A Protein-Cholesterol Interaction JAMES L. DUNCAN and RICHARD SCHLEGEL From the Departments of Microbiology and Pathology, Northwestern University Medical and Dental Schools, Chicago, Illinois 60611. Dr. Schlegel's present address is the Department of Pathology, Peter Bent Brigham Hospital, Harvard University Medical School, Boston, Massachusetts 02115. Downloaded from http://rupress.org/jcb/article-pdf/67/1/160/1266643/160.pdf by guest on 01 October 2021 ABSTRACT The effect of the bacterial cytolytic toxin, streptolysin O (SLO), on rabbit erythrocyte membranes, liposomes, and lipid dispersions was examined. SLO produced no gross alterations in the major erythrocyte membrane proteins or lipids. However, when erythrocytes were treated with SLO and examined by electron microscopy, rings and "C"-shaped structures were observed in the cell membrane. The rings had an electron-dense center, 24 nm in diameter, and the overall diameter of the structure was 38 nm. Ring formation also occurred when erythrocyte membranes were fixed with glutaraldehyde and OsO4 before the addition of toxin. In contrast, rings were not seen when erythrocytes were treated with toxin at 0~ indicating that adsorption of SLO to the membrane is not sufficient for ring formation since toxin is known to bind to erythrocytes at that temperature. The ring structures were present on lecithin-cholesterol-dicetylphos- phate liposomes after SLO treatment, but there was no release of the trapped, internal markers, K2CrO4 or glucose. The crucial role of cholesterol in the formation of rings and C's was demonstrated by the fact that these structures were present in toxin-treated cholesterol dispersions, but not in lecithin-dicetylphosphate dispersions nor in the SLO preparations alone. -
Biological Safety Guide
Biological Safety Guide Biological Safety Office Environmental Health & Safety Division 1405 Goss Lane, CI 1001 Augusta, Georgia 30912 Revised: February 2014 STATEMENT OF AUTHORITY Upon publication of these procedures, the Institutional Biosafety Committee (IBC) of the Georgia Regents University, is hereby authorized to act as agent for the Georgia Regents University in matters of review, control, and mediation arising from the use or proposed use of biological materials, including recombinant DNA, at the Georgia Regents University. A statement of composition of the Institutional Biosafety Committee and a delineation of authority is included in the following pages of this text. Furthermore, it is hereby declared that the Biological Safety Office of the Georgia Regents University derives its authority directly from the Office of the President of the Georgia Regents University in all matters involving biological safety and/or violations of accepted rules of practice as described herein. The Biosafety Officer is hereby granted the authority to immediately suspend a project which is found to be a threat to health, property, or the environment. ____________________________________ __________________ James J. Rush, Jr, Esq Date Chief Integrity Officer Georgia Regents University Georgia Regents University Biosafety Guide-January 2012 Statement of Authority TABLE OF CONTENTS List of Abbreviations .............................................................................. viii Forward ................................................................................................. -
From the Alfred I. Du Pont Institute, Wilmington, Deleware) Pr~S 33 ~O 41 (Received for Publication, January 7, 1957)
THE LEUKOTOXIC ACTION OF STREPTOCOCCI* Bx ARMINE T. WILSON, M.D. (From the Alfred I. du Pont Institute, Wilmington, Deleware) Pr~s 33 ~o 41 (Received for publication, January 7, 1957) This is the third study in a series on the interactions between streptococci and host cells. Previous reports have concerned the egestion of streptococci by phagocytic cells (1), and the failure of streptococci to lose their capacity of resisting phagocytosis after being killed with gentle heat or ultraviolet radiation (2). The present work is concerned with one type of outcome fol- lowing phagocytosis; namely, the destruction of the phagocytizing leuko- cytes which occurs when certain strains of streptococci are ingested. This injury will be called here "leukotoxic action," and the pertinent attribute of injurious streptococci will be called "leukotoxicity." It was described by Levaditi in 1918 (3), but has received no attention since that time as far as we have been able to discover. The leukotoxic effect is seen only after intact cocci have been phagocytized. It must not be confused with the action of streptococcal leukocidin, a soluble substance elaborated into the medium by growing cocci, which destroys leuko- cytes even when all coccal cells have been removed by filtration. Todd has presented impressive evidence indicating that leukocidin and streptolysin O are identical (4). In the present report consideration will be given to the biological charac- teristics of leukotoxicity, to its distribution among streptococci, its relation to other known streptococcal products, its relationship to virulence and its possible significance in streptococcal disease. Materials and Methods Strains.--Streptococei of the several serological groups and of types within group A have been accumulated from numerous sources, chiefly from Dr. -
Functional Consequences of Calcium Influx Promoted by Bacterial Pore
toxins Review Functional Consequences of Calcium Influx Promoted by Bacterial Pore-Forming Toxins Stéphanie Bouillot, Emeline Reboud and Philippe Huber * Université Grenoble Alpes, CNRS ERL5261, CEA BIG-BCI, INSERM UMR1036, Grenoble 38054, France; [email protected] (S.B.); [email protected] (E.R.) * Correspondence: [email protected] Received: 3 September 2018; Accepted: 20 September 2018; Published: 25 September 2018 Abstract: Bacterial pore-forming toxins induce a rapid and massive increase in cytosolic Ca2+ concentration due to the formation of pores in the plasma membrane and/or activation of Ca2+-channels. As Ca2+ is an essential messenger in cellular signaling, a sustained increase in Ca2+ concentration has dramatic consequences on cellular behavior, eventually leading to cell death. However, host cells have adapted mechanisms to protect against Ca2+ intoxication, such as Ca2+ efflux and membrane repair. The final outcome depends upon the nature and concentration of the toxin and on the cell type. This review highlights the repercussions of Ca2+ overload on the induction of cell death, repair mechanisms, cellular adhesive properties, and the inflammatory response. Keywords: host–pathogen interaction; bacterial virulence factor; cell death; signal transduction; ion flux Key Contribution: This review summarizes the numerous host cell alterations induced by Ca2+ overload triggered by bacterial pore-forming toxins, as well as the defense mechanisms implemented by the host to limit Ca2+ intoxication and plasma membrane perforation. 1. Introduction Bacterial pore-forming toxins (PFTs) are the most frequently encountered virulence factors among bacterial pathogens [1–4]. They are secreted in the extracellular milieu from Gram-negative and Gram-positive bacteria by various bacterial secretion systems.