Antimicrobial Chromogranin a Derived Peptides and Staphylococcus Aureus: from Host Pathogen Interaction Analysis to Development
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Antimicrobial chromogranin A derived peptides and Staphylococcus aureus : from host pathogen interaction analysis to development of antimicrobial polymer coating Rizwan Aslam To cite this version: Rizwan Aslam. Antimicrobial chromogranin A derived peptides and Staphylococcus aureus : from host pathogen interaction analysis to development of antimicrobial polymer coating. Medication. Université de Strasbourg, 2013. English. NNT : 2013STRAJ017. tel-01059511 HAL Id: tel-01059511 https://tel.archives-ouvertes.fr/tel-01059511 Submitted on 1 Sep 2014 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. UNIVERSITÉ DE STRASBOURG Ecole Doctorale Des Science De La Vie Et De La Santé (ED 414) Inserm UMR 1121 Biomatériaux et Bioingénierie THÈSE Présentée par : Rizwan ASLAM Soutenue le : 15 Avril 2013 Pour obtenir le grade de : Docteur de l’université de Strasbourg Discipline/ Spécialité : Aspects Moléculaire et Cellulaire de la Biologie Les peptides antimicrobiens dérivés de la chromogranine A et Staphylococcus aureus: de l’analyse de l’interaction hôte-pathogène au développement de revêtement de polymère antimicrobien THÈSE dirigée par : Mme METZ BOUTIGUE Marie Hélène Directrice de Recherche, Université de Strasbourg M. PREVOST Gilles MCU-PH, Université de Strasbourg RAPPORTEURS : M. DRIDER Djamel Pr, Université de Lille-1 M. BERJEAUD Jean-Marc Pr, Université de Poitiers M. BECHINGER Burkhard Pr, Université de Strasbourg AUTRES MEMBRES DU JURY : M. JACQUES Philippe Pr, Université de Lille-1 Acknowledgement I humbly bow my head before God, the most beneficent and merciful, whose blessing flourished my thoughts and thrived my ambitions. I could never have done this without the faith I have in You, the Almighty. I would like to express my deep and sincere gratitude to my supervisor, Dr. Marie Hélène METZ-BOUTIGUE, for making it possible for me to work in such a prestigious scientific environment. She has been very supportive, encouraging and kind. I owe a great deal of appreciation for her valuable advice, constructive criticism and extensive discussions around my work. It has been a great honor to have her as a supervisor. I feel immense pleasure to gratefully acknowledge and to express a deep sense of gratitude to my co-supervisor Dr. Gilles PRÉVOST for his creative suggestions, motivation and exemplary guidance throughout the course of my doctoral research and also during thesis writing. I wish to express my cordial appreciation to my examiners, Prof. Bukhard Bechinger, Prof. Djamel DRIDER, Prof. Jean-Marc BERJEAUD, and Prof. Philippe JACQUES for the acceptance to be a referee. I feel immense pleasure to gratefully acknowledge and to express a deep sense of gratitude to Prof. Pierre SCHAAF, Prof. Jean-Claude VOEGEL, Dr. Francis SCHNEIDER, Dr. Fouzia BOULMEDAIS, Dr. Alain VAN DORSSELAER, Dr. Jean-Marc STRUB, for their enthusiasm, creative suggestions and motivation throughout the course of my doctoral research. Moreover, I offer my profound gratitude to Prof. Youssef HAIKEL for his moral and financial support. Words are lacking to express my gratitude for Higher Education Commission of Pakistan and especially Dr. Atta ur Rehman, for providing me with a scholarship during my study in France. The opportunity of studying in France has really broadened my horizon and widened my perspectives in life. My sincere thanks are also extended to Dr. Jean Francois CHICH and Dr. Peiman SHOOSHTARIZADEH for their help in learning various techniques and to evaluate results more precisely and also offer them my zealous thanks. I also benefited by outstanding support of Bernard GUEROLD, for providing various synthetic peptides for my experiments. My heartfelt thanks are also extended to Dr. Philippe LAVALLE and Dr. Roxane FABRE for their expertise in confocal microscopy and offer my zealous thanks to Dr. Gwenaelle CADO and Lydie SEON for preparation of i multicoated PEM films. I would like to offer my gratitude to Dr. Benoît-Joseph LAVENTIE, Daniel KELLER, Mira TAWK and Raymonde GIRARDOT for support to complete flow cytometry analysis and providing bacterial strains and PMNs. I sincerely acknowledge my colleagues especially Dr. Atiandou M. Cynthia, Charlotte BACH, Martine RIVET, Cosette BETSCHA, Sophie HELLE, Merium SAHRAOUI, Dr. Céline MARBAN, Ouria TAHAR, and Qiongue Hu for their support during my projects and for facilitating all experimental or administrative issues. I own my sincere appreciations to Sultan ALI, and Ghulam HUSSAIN for their support, guidance and affection. I would also like to extend huge, warm thanks to my friends Asghar Shabbir, Azeem Sultan, Sarfraz Shafiq, Muhammad Nauman Zahid, Tariq Mahmood, Adnan Khan Niazi and Azhar Ayyaz Pirzadoo for their love and sincerity. I am eternally grateful to my beloved mother, my brothers and my sister for their unconditional love, fidelity, endurance and encouragement. I would like to thanks to a person whose ambidextrous nature made me more enthusiastic. There are so many others whom I may have inadvertently left out and I sincerely thank all of them for their help. ii Table of Contents Acknowledgements………………………………………………..………….. i Table of contents………………………………………………………………..……….iii Abbreviations………………………………………………………….………ix List of Figures…………………………………………………………………….……..xii List of Tables……………………………………………………………………………xiv Part I: Introduction 1 Staphylococcus aureus ................................................................................. - 19 - 1.1 Virulence factors of the S. aureus ....................................................................... - 20 - 1.1.1 Surface proteins ............................................................................................... - 21 - 1.1.1.1 Cell wall and capsular factors ................................................................ - 22 - 1.1.1.2 Microbial Surface Components Recognizing Adhesive Matrix Molecules (MSCRAMM) ......................................................................................................... - 22 - 1.1.1.2.1 Fibronectin binding proteins (A and B) ............................................. - 23 - 1.1.1.2.2 Protein A ............................................................................................ - 24 - 1.1.1.2.3 Collagen adhesion proteins ................................................................ - 24 - 1.1.1.2.4 Clumping factors (A and B) .............................................................. - 24 - 1.1.1.3 Secretable expanded repertoire adhesive molecules (SERAMs) ........... - 25 - 1.1.2 Secreted proteins ............................................................................................. - 26 - 1.1.2.1 Toxins .................................................................................................... - 26 - 1.1.2.1.1 Staphylococcal Enterotoxins ............................................................. - 26 - 1.1.2.1.2 Exfoliative toxins ............................................................................... - 28 - 1.1.2.1.3 Toxic shock syndrome toxins ............................................................ - 29 - 1.1.2.1.4 Staphylococcal Hemolysins ............................................................... - 31 - 1.1.2.1.4.1 Alpha hemolysin ......................................................................... - 31 - 1.1.2.1.4.2 Beta hemolysin ........................................................................... - 32 - 1.1.2.1.4.3 Gamma hemolysins .................................................................... - 32 - 1.1.2.1.4.4 Delta hemolysin .......................................................................... - 33 - 1.1.2.1.5 Panton valentine leucocidin ............................................................... - 33 - 1.1.2.1.6 Leukotoxin LukE/D ........................................................................... - 34 - 1.1.2.1.7 Other Bi-component cytolytic toxins ................................................ - 35 - iii 1.1.2.2 Proteases of S. aureus ............................................................................ - 35 - 1.2 Host defences against S.aureus infection ............................................................ - 36 - 1.3 Immune evasion strategies of S. aureus .............................................................. - 39 - 1.3.1 Resistance to phagocytosis .............................................................................. - 40 - 1.3.2 Complement inactivation ................................................................................ - 40 - 1.3.3 Inhibition of neutrophil chemotaxis ................................................................ - 42 - 1.3.4 Leukocytes destruction by toxins .................................................................... - 43 - 1.3.5 Resistance to lysozyme ................................................................................... - 44 - 1.3.6 Survival of S. aureus in neutrophil phagosomes ............................................. - 44 - 1.3.7 Subversion of the humoral immune response ................................................