DOCSLIB.ORG

Development of a Cholera Toxin Cta2/B Based Staphylococcus

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Development of a Cholera Toxin Cta2/B Based Staphylococcus DEVELOPMENT OF A CHOLERA TOXIN CTA2/B BASED STAPHYLOCOCCUS AUREUS VACCINE TO PREVENT BOVINE MASTITIS by Neha Misra A dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy in Biomolecular Sciences Boise State University December 2017 © 2017 Neha Misra ALL RIGHTS RESERVED BOISE STATE UNIVERSITY GRADUATE COLLEGE DEFENSE COMMITTEE AND FINAL READING APPROVALS of the dissertation submitted by Neha Misra Dissertation Title: Development of a Cholera Toxin Cta2/B-Based Staphylococcus Aureus Vaccine to Prevent Bovine Mastitis Date of Final Oral Examination: 24 October 2017 The following individuals read and discussed the dissertation submitted by student Neha Misra, and they evaluated her presentation and response to questions during the final oral examination. They found that the student passed the final oral examination. Juliette Tinker, Ph.D. Chair, Supervisory Committee Kenneth A. Cornell, Ph.D. Member, Supervisory Committee Julia Thom Oxford, Ph.D. Member, Supervisory Committee Mark A. McGuire, Ph.D. Member, Supervisory Committee Larry Fox, Ph.D. External examiner The final reading approval of the thesis was granted by Juliette Tinker, Ph.D., Chair of the Supervisory Committee. The dissertation was approved by the Graduate College. DEDICATION I dedicate this dissertation to my parents, who have been my inspiration. To my little sister, who never stopped encouraging me and to my husband for his endless support and love. iv " The important thing is not to stop questioning. Curiosity has its own reason for existing." Albert Einstein (1879-1955) v ACKNOWLEDGEMENTS My experience at Boise State University and especially Tinker’s lab has been nothing short of amazing. Since my first day on August 19th, 2013 I have felt at home at BSU. Today I would like to thank everyone who helped me in any form during my incredible journey toward obtaining a Ph.D. First and foremost, I would like to convey sincere gratitude and thanks to my advisor, Dr. Juliette Tinker for giving me the opportunity to work in her lab and for her continuous support, patience and motivation. I am truly blessed to have her as my advisor/mentor; she has a passion for science and research, which has induced effects on her students. She gave me full freedom and flexibility to design my own experiments, using new ideas. Her knowledge and guidance helped me in my research as well as thesis writing. She has not only encouraged me academically, but also emotionally through the rough road to finish this thesis. Her teachings go beyond academics; she taught me to be humble and generous even after being knowledgeable and talented. I would like to thank all my committee members Dr. Ken Cornell, Dr. Julie Oxford and Dr. Mark McGuire, for their expert suggestions, guidance and encouragement all these years. I want to give special thanks to Dr. Wingett for her support, career advice and encouragement. This thesis would not be as glorious without the help of Rebecca Hermann and her contributions in training me in flow cytometry. She not only helped me in my experiment but was also never tired of my endless questions. I also want to give special thanks to Dr. Shin Pu for his contributions with all mass spectrometry vi experiments and his patience in making me understand the results. I want to give a very special thanks to all present and past members of Tinker’s lab. Especially Tyler Wines for being a great friend and for all scientific discussions. Special thanks to Orion Thomson Vogel, Delaney Sauer, Eli Luna, Kristina Chapman, Colton Knopp, and Hannah Weaver for technical support. I want to also thank Rosey Whiting for being a great friend. Additionally, I would also like to thank Emily Price, Laura Rogers, Connor Richmond, Kimberly Brown and Liwen Yang. This acknowledgement page is incomplete without acknowledging my good friend Beth Gee. Her role in my Ph.D. and this program goes far beyond her duties as a program coordinator; she supported me and cheered for me at every milestone and success I achieved during this Ph.D. Last but not the least. I want to thank my loving and supportive husband, Hemant for his constant support, encouragement and suggestions. And I thank my parents, Dr. Suman Mishra and Anupama Mishra and my sister Meghna for their unconditional love and support. This thesis would not have been possible without them. vii ABSTRACT Staphylococcus aureus is an important pathogen causing chronic and invasive disease worldwide. This bacterium is a leading cause of community and hospital acquired infections in humans, and is also known to infect wild and domestic animals. Bovine mastitis, or inflammation of the udder, is one of the most economically relevant diseases of the dairy industry, with a high incidence worldwide. S. aureus is a major etiological agent causing this disease. S. aureus mastitis is highly contagious and difficult or impossible to treat. Management practices at dairy farms, that include good sanitation and antibiotic use, have been partially successful in reducing the occurrence of this disease, however, a complete prevention or elimination is still to be achieved. Despite efforts over more than two decades, an effective vaccine for S. aureus mastitis, that can protect against heterologous strains of this bacterium, is not yet available. These efforts however, have improved our understanding of the pathogenicity, virulence factor expression and immune responses to this bacterium. Studies have indicated that there is significant intraspecies variability, and an effective vaccine against S. aureus will require the incorporation of multiple conserved and relevant antigens. Additionally, the route of vaccine administration and use of adjuvants to aid in antigen delivery and enhancement of immune responses will also be critical. S. aureus contains a broad array of virulence factors required for colonization and disease, including: adhesins, toxins, a polysaccharide capsule, enzymes and immune evasion molecules, that are required for adhesion, invasion and colonization. Some viii virulence factors are highly conserved and centrally important for bacterial survival and sustenance, making them good vaccine targets. The iron-regulated surface determinant A (IsdA) and clumping factor A (ClfA) are two such conserved S. aureus extracellular- matrix adhesins that are promising vaccine antigens. However, an effective S. aureus vaccine for the prevention or reduction of mastitis will need to induce mucosal and systemic, as well as cellular and humoral, immune responses to these antigens. Bacterial enterotoxins are well characterized vaccine adjuvants that act by enhancing the mucosal delivery of antigens and promoting both systemic and mucosal humoral responses. Cholera toxin (CT), from Vibrio cholerae is a gold-standard vaccine adjuvant that can promote both humoral and cellular immune responses to co-administered antigens when delivered to mucosal surfaces. The work presented here is based upon the overarching hypothesis that a mucosal, enterotoxin-based vaccine containing multiple relevant antigens will protect cows against S. aureus mastitis. To construct this vaccine, three immediate aims were developed. First, to ensure the incorporation of relevant antigens, the variability, genetic conservation and immunogenicity of the IsdA protein during bovine infection was determined. Second, a cholera toxin adjuvant based vaccine containing IsdA and a second antigen, ClfA (IsdA-CTA2/B +ClfA-CTA2/B) was used to vaccinate cows to determine immunogenicity. Lastly, a new immunoproteomics approach was used to identify immunogenic antigens for future incorporation into a multivalent vaccine. The results from these studies, as presented in chapters 2-4, indicate that: 1) the IsdA adhesin is expressed and conserved in bovine strains of S. aureus, 2) IsdA-CTA2/B + ClfA-CTA2/B can stimulate significant immune responses in vaccinated animals after intranasal ix administration and 3) immunoproteomics using milk antibodies can be used to identify new potential S. aureus vaccine antigens. The studies presented here will contribute to the advancement and understanding of staphylococcal vaccines in general, and specifically to those that will prevent bovine mastitis. x TABLE OF CONTENTS DEDICATION ................................................................................................................... iv ACKNOWLEDGEMENTS ............................................................................................... vi ABSTRACT ..................................................................................................................... viii LIST OF TABLES .............................................................................................................xv LIST OF FIGURES ......................................................................................................... xvi LIST OF ABBREVIATIONS ......................................................................................... xxii CHAPTER ONE: CHARACTERIZATION OF STAPHYLOCOCCUS AUREUS INFECTION AND ITS PREVENTION BY VACCINE ....................................................1 Background and Introduction ..................................................................................1 Staphylococcus Aureus “the super bug” ......................................................1 Virulence and Pathogenicity of S. aureus ....................................................3 S. aureus Vaccine Antigens and Vaccines .................................................10
Load more

Recommended publications
  • Host-Pathogen Interactions of Secreted and Surface Staphylococcus Aureus Factors
    The Texas Medical Center Library DigitalCommons@TMC The University of Texas MD Anderson Cancer Center UTHealth Graduate School of The University of Texas MD Anderson Cancer Biomedical Sciences Dissertations and Theses Center UTHealth Graduate School of (Open Access) Biomedical Sciences 5-2010 Host-pathogen interactions of secreted and surface Staphylococcus aureus factors Vanessa Vazquez Follow this and additional works at: https://digitalcommons.library.tmc.edu/utgsbs_dissertations Part of the Biochemistry Commons, and the Microbiology Commons Recommended Citation Vazquez, Vanessa, "Host-pathogen interactions of secreted and surface Staphylococcus aureus factors" (2010). The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences Dissertations and Theses (Open Access). 25. https://digitalcommons.library.tmc.edu/utgsbs_dissertations/25 This Dissertation (PhD) is brought to you for free and open access by the The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences at DigitalCommons@TMC. It has been accepted for inclusion in The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences Dissertations and Theses (Open Access) by an authorized administrator of DigitalCommons@TMC. For more information, please contact [email protected]. Host-pathogen interactions of secreted and surface Staphylococcus aureus factors by Vanessa Vazquez, B.S. APPROVED: Supervisory Professor Magnus Höök, Ph.D. Burton Dickey, M.D. Theresa Koehler, Ph.D. C. Wayne Smith, M.D. Yi Xu, Ph.D. APPROVED: Dean, The University of Texas Health Science Center at Houston Graduate School of Biomedical Sciences HOST-PATHOGEN INTERACTIONS OF SECRETED AND SURFACE STAPHYLOCOCCUS AUREUS FACTORS A Dissertation Presented to the Faculty of The University of Texas Health Science Center at Houston and The University of Texas M.D.
    [Show full text]
  • Fibrinogen Binding Sites P336 and Y338 of Clumping Factor a Are Crucial for Staphylococcus Aureus Virulence
    Fibrinogen Binding Sites P336 and Y338 of Clumping Factor A Are Crucial for Staphylococcus aureus Virulence Elisabet Josefsson1*, Judy Higgins2, Timothy J. Foster2, Andrej Tarkowski1 1 Department of Rheumatology and Inflammation Research, University of Gothenburg, Go¨teborg, Sweden, 2 Microbiology Department, Moyne Institute of Preventive Medicine, Trinity College, Dublin, Ireland Abstract We have earlier shown that clumping factor A (ClfA), a fibrinogen binding surface protein of Staphylococcus aureus,isan important virulence factor in septic arthritis. When two amino acids in the ClfA molecule, P336 and Y338, were changed to serine and alanine, respectively, the fibrinogen binding property was lost. ClfAP336Y338 mutants have been constructed in two virulent S. aureus strains Newman and LS-1. The aim of this study was to analyze if these two amino acids which are vital for the fibrinogen binding of ClfA are of importance for the ability of S. aureus to generate disease. Septic arthritis or sepsis were induced in mice by intravenous inoculation of bacteria. The clfAP336Y338 mutant induced significantly less arthritis than the wild type strain, both with respect to severity and frequency. The mutant infected mice developed also a much milder systemic inflammation, measured as lower mortality, weight loss, bacterial growth in kidneys and lower IL-6 levels. The data were verified with a second mutant where clfAP336 and Y338 were changed to alanine and serine respectively. When sepsis was induced by a larger bacterial inoculum, the clfAP336Y338 mutants induced significantly less septic death. Importantly, immunization with the recombinant A domain of ClfAP336SY338A mutant but not with recombinant ClfA, protected against septic death.
    [Show full text]
  • Rope Parasite” the Rope Parasite Parasites: Nearly Every AuSC Child I Ever Treated Proved to Carry a Significant Parasite Burden
    Au#sm: 2015 Dietrich Klinghardt MD, PhD Infec4ons and Infestaons Chronic Infecons, Infesta#ons and ASD Infec4ons affect us in 3 ways: 1. Immune reac,on against the microbes or their metabolic products Treatment: low dose immunotherapy (LDI, LDA, EPD) 2. Effects of their secreted endo- and exotoxins and metabolic waste Treatment: colon hydrotherapy, sauna, intes4nal binders (Enterosgel, MicroSilica, chlorella, zeolite), detoxificaon with herbs and medical drugs, ac4vaon of detox pathways by solving underlying blocKages (methylaon, etc.) 3. Compe,,on for our micronutrients Treatment: decrease microbial load, consider vitamin/mineral protocol Lyme, Toxins and Epigene#cs • In 2000 I examined 10 au4s4c children with no Known history of Lyme disease (age 3-10), with the IgeneX Western Blot test – aer successful treatment. 5 children were IgM posi4ve, 3 children IgG, 2 children were negave. That is 80% of the children had clinical Lyme disease, none the history of a 4cK bite! • Why is it taking so long for au4sm-literate prac44oners to embrace the fact, that many au4s4c children have contracted Lyme or several co-infec4ons in the womb from an oVen asymptomac mother? Why not become Lyme literate also? • Infec4ons can be treated without the use of an4bio4cs, using liposomal ozonated essen4al oils, herbs, ozone, Rife devices, PEMF, colloidal silver, regular s.c injecons of artesunate, the Klinghardt co-infec4on cocKtail and more. • Symptomac infec4ons and infestaons are almost always the result of a high body burden of glyphosate, mercury and aluminum - against the bacKdrop of epigene4c injuries (epimutaons) suffered in the womb or from our ancestors( trauma, vaccine adjuvants, worK place related lead, aluminum, herbicides etc., electromagne4c radiaon exposures etc.) • Most symptoms are caused by a confused upregulated immune system (molecular mimicry) Toxins from a toxic environment enter our system through damaged boundaries and membranes (gut barrier, blood brain barrier, damaged endothelium, etc.).
    [Show full text]
  • Evaluation of the Efficacy of a Cholera Toxin-Based Staphylococcus
    Article Evaluation of the Efficacy of a Cholera Toxin-Based Staphylococcus aureus Vaccine against Bovine Intramammary Challenge Hussain A. Alabdullah 1,†, Elise Overgaard 2,† , Danielle Scarbrough 2, Janet E. Williams 1 , Omid Mohammad Mousa 3 , Gary Dunn 3, Laura Bond 4 , Mark A. McGuire 1 and Juliette K. Tinker 2,3,* 1 Department of Animal and Veterinary Science, University of Idaho, Moscow, ID 83844, USA; [email protected] (H.A.A.); [email protected] (J.E.W.); [email protected] (M.A.M.) 2 Biomolecular Sciences Graduate Program, Boise State University, Boise, ID 83725, USA; [email protected] (E.O.); [email protected] (D.S.) 3 Department of Biological Sciences, Boise State University, Boise, ID 83725, USA; [email protected] (O.M.M.); [email protected] (G.D.) 4 Biomolecular Research Center, Boise State University, Boise, ID 83725, USA; [email protected] * Correspondence: [email protected] † The authors contribute equally. Abstract: Staphylococcus aureus (S. aureus) is a primary agent of bovine mastitis and a source of signifi- cant economic loss for the dairy industry. We previously reported antigen-specific immune induction in the milk and serum of dairy cows following vaccination with a cholera toxin A2 and B subunit (CTA2/B) based vaccine containing the iron-regulated surface determinant A (IsdA) and clumping factor A (ClfA) antigens of S. aureus (IsdA + ClfA-CTA2/B). The goal of the current study was to assess the efficacy of this vaccine to protect against S. aureus infection after intramammary chal- lenge. Six mid-lactation heifers were randomized to vaccinated and control groups.
    [Show full text]
  • Frequency of Staphylococcus Aureus Virulence Genes in Milk of Cows and Goats with Mastitis1 Atzel C
    Pesq. Vet. Bras. 38(11):2029-2036, novembro 2018 DOI: 10.1590/1678-5150-PVB-5786 Original Article Animais de Produção/Livestock Diseases ISSN 0100-736X (Print) ISSN 1678-5150 (Online) PVB-5786 LD Frequency of Staphylococcus aureus virulence genes in milk of cows and goats with mastitis1 Atzel C. Acosta2*, Pollyanne Raysa F. Oliveira2, Laís Albuquerque2, Isamara F. Silva3, Elizabeth S. Medeiros2, Mateus M. Costa3, José Wilton Pinheiro Junior2 and Rinaldo A. Mota2 ABSTRACT.- Acosta A.C., Oliveira P.R.F., Albuquerque L., Silva I.F., Medeiros E.S., Costa M.M., Pinheiro Junior J.W. & Mota R.A. 2018. Frequency of Staphylococcus aureus virulence genes in milk of cows and goats with mastites. Pesquisa Veterinária Brasileira 38(11):2029-2036. Laboratório de Bacterioses dos Animais Domésticos, Departamento de Medicina Veterinária, Universidade Federal Rural de Pernambuco, Rua Dom Manoel de Medeiros s/n, Dois Irmãos, Frequency of Staphylococcus aureus virulence Recife, PE 52171-900, Brazil. E-mail: [email protected] genes in milk of cows and goats with mastitis The present study determined the frequency of Staphylococcus aureus virulence genes in 2,253 milk samples of cows (n=1000) and goats (n=1253) raised in three different geographical regions of the state Pernambuco, Brazil. The presence of genes of virulence [Frequency of Staphylococcus aureus virulence genes in factors associated to adhesion to host cells (fnbA, fnbB, clfA and clfB), toxinosis (sea, seb, sec, milk of cows and goats with mastites]. sed, seg, seh, sei, tsst, hla and hlb), and capsular polysaccharide (cap5 and cap8) was evaluated by PCR. A total of 123 and 27 S.
    [Show full text]
  • Staphylococcal Manipulation of Host Immune Responses
    REVIEWS Staphylococcal manipulation of host immune responses Vilasack Thammavongsa1,2, Hwan Keun Kim1, Dominique Missiakas1 and Olaf Schneewind1 Abstract | Staphylococcus aureus, a bacterial commensal of the human nares and skin, is a frequent cause of soft tissue and bloodstream infections. A hallmark of staphylococcal infections is their frequent recurrence, even when treated with antibiotics and surgical intervention, which demonstrates the bacterium’s ability to manipulate innate and adaptive immune responses. In this Review, we highlight how S. aureus virulence factors inhibit complement activation, block and destroy phagocytic cells and modify host B cell and T cell responses, and we discuss how these insights might be useful for the development of novel therapies against infections with antibiotic resistant strains such as methicillin-resistant S. aureus. 4 Abscesses Approximately 30% of the human population is contin- signals (that is, chemoattractants and cytokines ). The pathological product of uously colonized with Staphylococcus aureus, whereas Staphylococcal products are detected by immune cells Staphylococcus aureus some individuals are hosts for intermittent colonization1. via Toll-like receptors (TLRs) and G protein-coupled infection: the harbouring of S. aureus typically resides in the nares but is also found receptors, whereas cytokines activate cognate immune a staphylococcal abscess on the skin and in the gastrointestinal tract. Although receptors. Neutrophils answer this call, extravasate from community within a pseudocapsule of fibrin colonization is not a prerequisite for staphylococcal blood vessels, and migrate towards the site of infection deposits that is surrounded by disease, colonized individuals more frequently acquire to phagocytose and kill bacteria or to immobilize and layers of infiltrating immune infections1.
    [Show full text]
  • 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 .................................................................................................
    [Show full text]
  • Bioterrorism
    BIOTERRORISM Edited by Stephen A. Morse Bioterrorism Edited by Stephen A. Morse Published by InTech Janeza Trdine 9, 51000 Rijeka, Croatia Copyright © 2012 InTech All chapters are Open Access distributed under the Creative Commons Attribution 3.0 license, which allows users to download, copy and build upon published articles even for commercial purposes, as long as the author and publisher are properly credited, which ensures maximum dissemination and a wider impact of our publications. After this work has been published by InTech, authors have the right to republish it, in whole or part, in any publication of which they are the author, and to make other personal use of the work. Any republication, referencing or personal use of the work must explicitly identify the original source. As for readers, this license allows users to download, copy and build upon published chapters even for commercial purposes, as long as the author and publisher are properly credited, which ensures maximum dissemination and a wider impact of our publications. Notice Statements and opinions expressed in the chapters are these of the individual contributors and not necessarily those of the editors or publisher. No responsibility is accepted for the accuracy of information contained in the published chapters. The publisher assumes no responsibility for any damage or injury to persons or property arising out of the use of any materials, instructions, methods or ideas contained in the book. Publishing Process Manager Sasa Leporic Technical Editor Teodora Smiljanic Cover Designer InTech Design Team First published March, 2012 Printed in Croatia A free online edition of this book is available at www.intechopen.com Additional hard copies can be obtained from [email protected] Bioterrorism, Edited by Stephen A.
    [Show full text]
  • Botulinum Toxin
    Botulinum toxin From Wikipedia, the free encyclopedia Jump to: navigation, search Botulinum toxin Clinical data Pregnancy ? cat. Legal status Rx-Only (US) Routes IM (approved),SC, intradermal, into glands Identifiers CAS number 93384-43-1 = ATC code M03AX01 PubChem CID 5485225 DrugBank DB00042 Chemical data Formula C6760H10447N1743O2010S32 Mol. mass 149.322,3223 kDa (what is this?) (verify) Bontoxilysin Identifiers EC number 3.4.24.69 Databases IntEnz IntEnz view BRENDA BRENDA entry ExPASy NiceZyme view KEGG KEGG entry MetaCyc metabolic pathway PRIAM profile PDB structures RCSB PDB PDBe PDBsum Gene Ontology AmiGO / EGO [show]Search Botulinum toxin is a protein and neurotoxin produced by the bacterium Clostridium botulinum. Botulinum toxin can cause botulism, a serious and life-threatening illness in humans and animals.[1][2] When introduced intravenously in monkeys, type A (Botox Cosmetic) of the toxin [citation exhibits an LD50 of 40–56 ng, type C1 around 32 ng, type D 3200 ng, and type E 88 ng needed]; these are some of the most potent neurotoxins known.[3] Popularly known by one of its trade names, Botox, it is used for various cosmetic and medical procedures. Botulinum can be absorbed from eyes, mucous membranes, respiratory tract or non-intact skin.[4] Contents [show] [edit] History Justinus Kerner described botulinum toxin as a "sausage poison" and "fatty poison",[5] because the bacterium that produces the toxin often caused poisoning by growing in improperly handled or prepared meat products. It was Kerner, a physician, who first conceived a possible therapeutic use of botulinum toxin and coined the name botulism (from Latin botulus meaning "sausage").
    [Show full text]
  • Redalyc.Virulence Factors Analysis of Staphylococcus Aureus Isolated
    e-Gnosis E-ISSN: 1665-5745 [email protected] Universidad de Guadalajara México Franco G., Julio C.; González V., Libertad; Gómez M., Sandra C.; Carrillo G., Juan M.; Ramírez C., José J. Virulence factors analysis of Staphylococcus aureus isolated from bovine mastitis in México e-Gnosis, vol. 6, 2008, pp. 1-9 Universidad de Guadalajara Guadalajara, México Available in: http://www.redalyc.org/articulo.oa?id=73011197007 How to cite Complete issue Scientific Information System More information about this article Network of Scientific Journals from Latin America, the Caribbean, Spain and Portugal Journal's homepage in redalyc.org Non-profit academic project, developed under the open access initiative ©2008, e­Gnosis [online] Vol. 6, Art. 7 Virulence factors analysis of Staphylococcus aureus isolated from bovine mastitis in México … Franco J.C. et. al. Análisis de los factores de virulencia de Staphylococcus aureus aislados de mastitis bovina en México Virulence factors analysis of Staphylococcus aureus isolated from bovine mastitis in México Julio C. Franco G.1, Libertad González V.1, Sandra C. Gómez M.1, Juan M. Carrillo G.2 and José J. Ramírez C.1 [email protected] / [email protected] [email protected] / [email protected] [email protected] / / Recibido: agosto 27, 2008 / Aceptado: noviembre 8 , 2008 / Publicado: noviembre 20, 2008 1Unidad de Biotecnología, Centro de Investigación y Asistencia en Tecnología y Diseño del Estado de Jalisco A. C. (CIATEJ). Normalistas 800, Colinas de la Normal, C.P. 44270 Guadalajara, Jalisco, México. 2Laboratorios Veterinarios HALVET S.A. de C. V. Gabriel Castaños 85, CP 44130 Guadalajara, Jalisco México.
    [Show full text]
  • B-Neurexin Is a Ligand for the Staphylococcus Aureus MSCRAMM Sdrc
    b-Neurexin Is a Ligand for the Staphylococcus aureus MSCRAMM SdrC E. Magda Barbu1,2, Vannakambadi K. Ganesh1, Shivasankarappa Gurusiddappa1, R. Chris Mackenzie2, Timothy J. Foster3, Thomas C. Sudhof4, Magnus Ho¨ o¨ k1* 1 Center for Infectious & Inflammatory Diseases, Institute of Biosciences and Technology, Texas A&M Health Science Center, Houston, Texas, United States of America, 2 Microbiology and Molecular Genetics Department, University of Texas Health Science Center at Houston, Houston, Texas, United States of America, 3 Moyne Institute of Preventive Medicine, Department of Microbiology, Trinity College, Dublin, Ireland, 4 Neuroscience Institute, Department of Molecular and Cellular Physiology, Stanford University, Palo Alto, California, United States of America Abstract Gram-positive bacteria contain a family of surface proteins that are covalently anchored to the cell wall of the organism. These cell-wall anchored (CWA) proteins appear to play key roles in the interactions between pathogenic organisms and the host. A subfamily of the CWA has a common structural organization with multiple domains adopting characteristic IgG-like folds. The identified microbial surface components recognizing adhesive matrix molecules (MSCRAMMs) belong to this subfamily, as does SdrC from S. aureus. However, an interactive host ligand for the putative MSCRAMM SdrC was not previously identified. We have screened a phage display peptide library and identified a peptide sequence found in b- neurexin that binds SdrC. A synthetic peptide corresponding to the identified sequence as well as a recombinant form of the b-neurexin 1 exodomain binds SdrC with high affinity and specificity. Furthermore, expression of SdrC on bacteria greatly enhances microbial adherence to cultured mammalian cells expressing b-neurexin on their surface.
    [Show full text]
  • Preclinical Efficacy of Clumping Factor a in Prevention of Staphylococcus Aureus Infection
    Preclinical Efficacy of Clumping Factor A in Prevention of Staphylococcus aureus Infection The Harvard community has made this article openly available. Please share how this access benefits you. Your story matters Citation Li, Xue, Xiaogang Wang, Christopher D. Thompson, Saeyoung Park, Wan Beom Park, and Jean C. Lee. 2016. “Preclinical Efficacy of Clumping Factor A in Prevention of Staphylococcus aureus Infection.” mBio 7 (1): e02232-15. doi:10.1128/mBio.02232-15. http:// dx.doi.org/10.1128/mBio.02232-15. Published Version doi:10.1128/mBio.02232-15 Citable link http://nrs.harvard.edu/urn-3:HUL.InstRepos:25658431 Terms of Use This article was downloaded from Harvard University’s DASH repository, and is made available under the terms and conditions applicable to Other Posted Material, as set forth at http:// nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of- use#LAA RESEARCH ARTICLE crossmark Preclinical Efficacy of Clumping Factor A in Prevention of Staphylococcus aureus Infection Xue Li,a,b Xiaogang Wang,a Christopher D. Thompson,a Saeyoung Park,a* Wan Beom Park,a,c Jean C. Leea Division of Infectious Diseases, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts, USAa; Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, Chinab; Department of Internal Medicine, Seoul National University College of Medicine, Seoul, South Koreac * Present address: Saeyoung Park, Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, USA. ABSTRACT Treatment of Staphylococcus aureus infections has become increasingly difficult because of the emergence of multidrug-resistant isolates.
    [Show full text]