Bacterial Outer Membrane Vesicles. Mediators of virulence and antibiotic resistance. Schaar, Viveka 2013 Link to publication Citation for published version (APA): Schaar, V. (2013). Bacterial Outer Membrane Vesicles. Mediators of virulence and antibiotic resistance. [Doctoral Thesis (compilation), Clinical Microbiology, Malmö]. Medical Microbiology, Lund University. 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LUND UNIVERSITY PO Box 117 221 00 Lund +46 46-222 00 00 Download date: 01. Jan. 2023 Bacterial Outer Membrane Vesicles Mediators of virulence and antibiotic resistance by due permission of the Faculty of Medicine, Lund University, Sweden. To be defended at the main lecture hall of the Pathology building, Skåne University Hospital Malmö, on Friday October 18th 2013 at 13:00. Faculty opponent Assistant Professor Anders P. Håkansson, Department of Microbiology and Immunology University at Buffalo, the State University of New York, Buffalo, New York, USA 1 Organization Document name LUND UNIVERSITY Date of issue Author(s) Sponsoring organization Title and subtitle Abstract Key words Classification system and/or index terms (if any) Supplementary bibliographical information Language ISSN and key title 1652-8220 ISBN 978-91-87449-83-3 Recipient’s notes Number of pages Price Security classification Signature Date 2 Bacterial Outer Membrane Vesicles Mediators of virulence and antibiotic resistance Viveka Schaar 3 © 2013 Viveka Schaar Lund University, Faculty of Medicine Department of Laboratory Medicine, Malmö Doctoral Dissertation Series 2013:111 ISBN 978-91-87449-83-3 ISSN 1652-8220 Cover photo: Manipulated TEM image of OMV-secreting Moraxella catarrhalis, reprinted with permission from Oxford University Press and Springer Science Printed in Sweden by Media-Tryck, Lund University Lund 2013 4 Till Absent Friends 5 6 Table of Contents Table of Contents 7 List of papers 9 Abbreviations 11 Populärvetenskaplig sammanfattning 13 Introduction 15 Respiratory Tract Infections 15 Anatomy of the respiratory tract 15 Upper respiratory tract infections 16 Lower respiratory tract infections 16 Pathogens & Host Immunity 19 Bacteria 19 Innate immunity 20 Adaptive immunity 22 Immunity and bacterial infections 23 The Pathogens 25 Moraxella catarrhalis 25 Haemophilus influenzae 28 Streptococcus pneumoniae and group A streptococci 28 Nasopharyngeal co-infections 29 Outer Membrane Vesicles 31 Biogenesis 32 Characterization and composition 33 Cell interactions 34 Biofilms and vaccines 35 Pathogens & Antimicrobial Resistance 37 Antimicrobial drugs 37 Antibiotic resistance 38 Testing for antibiotic susceptibility and resistance 39 M. catarrhalis and H. influenzae resistance against β-lactam antibiotics 39 The present investigation 43 7 Aims 43 Results and Discussion 44 Paper I 44 Paper II 47 Paper III 48 Paper IV 50 Conclusions 52 Future perspectives 53 Acknowledgements 56 References 58 Paper I-IV 75 8 List of papers Schaar, V., de Vries, S.P., Perez Vidakovics, M.L., Bootsma, H.J., Larsson, L., Hermans, P.W., Bjartell, A., Mörgelin, M. and Riesbeck K. (2011). Multicomponent Moraxella catarrhalis outer membrane vesicles induce an inflammatory response and are internalized by human epithelial cells. Cellular Microbiology 13, 432-449. Schaar, V., Nordström, T., Mörgelin, M. and Riesbeck, K. (2011). Moraxella catarrhalis outer membrane vesicles carry beta-lactamase and promote survival of Streptococcus pneumonia and Haemophilus influenzae by inactivating amoxicillin. Antimicrobial Agents and Chemotherapy 55(8): 3845-53. Schaar, V., Paulsson M., Mörgelin, M. and Riesbeck, K. (2012) Outer membrane vesicles shield Moraxella catarrhalis -lactamase from neutralization by serum IgG. Journal of Antimicrobial Chemotherapy 68(3): 593-600. Schaar, V., Uddbäck I., Nordström T., and Riesbeck, K. (2013) Group A Streptococci are protected from amoxicillin-mediated killing by vesicles containing β-lactamase derived from Haemophilus influenzae. Journal of Antimicrobial Chemotherapy, Aug 2, in press. The published papers are reproduced with permission from respective copyright holder; Paper I from John Wiley & Sons Ltd., Paper II from the American Society of Microbiology, Paper III and Paper IV from Oxford University Press. 9
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