University of New Hampshire University of New Hampshire Scholars' Repository Doctoral Dissertations Student Scholarship Winter 1989 Pathogenesis, pathology and chemotherapy of experimental Legionella pneumophila infection Arthur O. Tzianabos University of New Hampshire, Durham Follow this and additional works at: https://scholars.unh.edu/dissertation Recommended Citation Tzianabos, Arthur O., "Pathogenesis, pathology and chemotherapy of experimental Legionella pneumophila infection" (1989). Doctoral Dissertations. 1601. https://scholars.unh.edu/dissertation/1601 This Dissertation is brought to you for free and open access by the Student Scholarship at University of New Hampshire Scholars' Repository. It has been accepted for inclusion in Doctoral Dissertations by an authorized administrator of University of New Hampshire Scholars' Repository. For more information, please contact [email protected]. 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Ann Arbor, MI 48106 PATHOGENESIS, PATHOLOGY AND CHEMOTHERAPY OF EXPERIMENTAL LEGIONELLA PNEUMOPHILA INFECTION BY ARTHUR O. TZIANABOS B.S. BOSTON COLLEGE, 1985 DISSERTATION Submitted to the University of New Hampshire in Partial Fulfillment of the Requirements for the Degree of Doctor of Philosophy in Microbiology December, 1989 This dissertation has been examined and approved. Dissertation director, Dr\ Frank G. Rodgers Associate Professor of Microbiology Dr. William R. ChesbroyProf^ssor of Microbiology Dr. Donald M. Green, Professor of Biochemistry )h Jr Moore Jl nd Nutritional Dr. Thomas G. Pistole, Professor of Microbiology ~2.g fsUvleH&eg, \ ^ °\ Date TO MY PARENTS Acknowledgments I wish to thank the Research Office and Graduate School of the University of New Hampshire for their support in the form of research funds, teaching and dissertation fellowships during my graduate studies. These years have brought som e of the most exhilarating and difficult times I have yet known. During this endeavor, I have had the pleasure of working with some great people: I express my deepest gratitude to my advisor, Dr. Frank Rodgers, for his instruction, advice and constant encouragement throughout the course of this investigation. I shall value what I have learned from him. I also thank the members of my doctoral committee, Dr. William Chesbro, Dr. Donald Green, Dr. Joe Moore and Dr. Tom Pistole, for their guidance and helpful suggestions. I am indebted to Bob Mooney for his expertise and friendship during our many discussions of matters scientific and not so scientific. Thanks go to Linda Dibernardo and Alberta Moulton for their help and patience, members of Dr. Rodgers' lab for their useful discussion, and to fellow graduate students, Robin Ross, Bob Millham and Tod Gavron for their corrupting influence. I also thank Kirsten Quist for her love and forbearance during the last year. Finally, I thank my parents for all of their love and support. I am forever grateful. TABLE OF CONTENTS page DEDICATION.................................................................................................................. iii ACKNOWLEDGMENTS................................................................................................ iv LIST OF TABLES............................................................................................................ vii LIST OF FIGURES......................................................................................................... ix LIST OF PLATES............................................................................................................ xii ABSTRACT...................................................................................................................... xv FRONTISPIECE........................................................................................................... xvii SECTION page I. NATURAL HISTORY of LEGIONNAIRES' DISEASE............................. 1 1.1 Preface................................................................................................. 1 1.2 Historical perspective ......................................................................... 1 1.3 The Organism....................................................................................... 4 1.3.1 Taxonomy and nomenclature .......................................................... 4 1.3.2 Morphological characteristics.......................................................... 7 1.3.3 Biochemical properties..................................................................... 10 1.3.4 Physico-chemical properties ............................................................ 13 1.3.5 Genetics ............................................................................................... 13 1.3.6 Environmental aspects ...................................................................... 15 1.4 The Disease........................................................................................ 16 1.4.1 Epidemiology....................................................................................... 16 1.4.2 Clinical features ................................................................................... 24 1.4.3 Pathology.............................................................................................. 25 1.4.4 Pathogenesis....................................................................................... 27 1.4.5 Diagnosis.............................................................................................. 28 1.4.6 Immunity ............................................................................................... 31 1.4.7 Antimicrobial therapy ......................................................................... 33 v II. HYPOTHESIS and SPECIFIC AIMS ............................................................ 35 III. PARTIAL CHARACTERIZATION of LEGIONELLA PNEUMOPHILA ADHERENCE TO HOST CELLS................................................................... 37 3.1 Abstract........................................................................................................ 37 3.2 Introduction .................................................................................................. 38 3.3 Materials and Methods .............................................................................. 41 3.4 Results.......................................................................................................... 47 3.5 Discussion .................................................................................................... 50 IV. THE EFFECT OF ANTIBIOTICS THAT INHIBIT CELL WALL, PROTEIN AND DNA SYNTHESIS on the GROWTH and MORPHOLOGY OF LEGIONELLA PNEUMOPHILA................................ 77 4.1 Abstract........................................................................................................ 77 4.2 Introduction ................................................................................................. 78 4.3 Materials and Methods ............................................................................. 79 4.4 Results......................................................................................................... 81 4.5 Discussion .................................................................................................... 85 V. PATHOGENESIS, PATHOLOGY and CHEMOTHERAPY of EXPERIMENTAL LEGIONELLA PNEUMOPHILA INFECTION in the CHICK EMBRYO .................................................................................... 118 5.1 Abstract........................................................................................................ 118 5.2 Introduction.................................................................................................. 120 5.3 Materials and Methods ............................................................................