Antimicrobial Resistant Escherichia Coli in Alberta's Rural Well Water
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University of Calgary PRISM: University of Calgary's Digital Repository Graduate Studies The Vault: Electronic Theses and Dissertations 2017 Antimicrobial Resistant Escherichia coli in Alberta's Rural Well Water Meyer, Kelsey Meyer, K. (2017). Antimicrobial Resistant Escherichia coli in Alberta's Rural Well Water (Unpublished master's thesis). University of Calgary, Calgary, AB. doi:10.11575/PRISM/24938 http://hdl.handle.net/11023/3976 master thesis University of Calgary graduate students retain copyright ownership and moral rights for their thesis. You may use this material in any way that is permitted by the Copyright Act or through licensing that has been assigned to the document. For uses that are not allowable under copyright legislation or licensing, you are required to seek permission. Downloaded from PRISM: https://prism.ucalgary.ca UNIVERSITY OF CALGARY Antimicrobial Resistant Escherichia coli in Alberta’s Rural Well Water by Kelsey Meyer A THESIS SUBMITTED TO THE FACULTY OF GRADUATE STUDIES IN PARTIAL FULFILMENT OF THE REQUIREMENTS FOR THE DEGREE OF MASTER OF SCIENCE GRADUATE PROGRAM IN MICROBIOLOGY AND INFECTIOUS DISEASES CALGARY, ALBERTA JULY, 2017 © Kelsey Meyer 2017 Abstract The consumption of rural well water (RWW) contaminated with antimicrobial resistant (AMR) Escherichia coli has been linked to human carriage of resistance. Our objective was to determine whether AMR and extended spectrum beta lactamase (ESBL) producing E.coli are present in Alberta’s RWW. Resistant isolates were detected with an agar screen on (up to) 20 isolates from each sample, and AMR was measured with NARMS Sensititre™ panels. Disk diffusion assays detected ESBL-producing E.coli, and spatial clusters of AMR E.coli were assessed using ArcGIS (version 10.4.1) and SaTScan™ (version 9.4.4). Among 1129 samples, 22% contained AMR E.coli including four ESBL-producers. Resistance to three or more classes of antimicrobials was observed in 48% of AMR E.coli isolates, and a significant cluster of AMR E.coli was detected between Calgary and Lethbridge (p<0.05). Our results suggest AMR and ESBL-producing E.coli are present in Alberta’s rural well water, posing a risk to human and animal health. ii Acknowledgements This thesis would not have been possible without the incredible inspiration and support I received from so many individuals – thank you all for your contributions to my thesis and for being a part of this journey. I owe my deepest gratitude to my supervisor, Dr. Sylvia Checkley, for her unwavering support throughout my degree, for encouraging my academic growth, but also my career development and personal growth. Her continuous support, patience, and knowledge led me to where I am today, and I am so grateful to have had such a caring and encouraging supervisor. I would also like to thank my committee members, Dr. Rebekah DeVinney and Dr. Karen Liljebjelke, for their insight and encouragement throughout my studies. Without their knowledge and guidance, this thesis would not have been possible. Thank you to Dr. Marie Louie for her support, knowledge, and career guidance, and for opening my eyes to the world of clinical microbiology. I would also like to acknowledge the generous contributions of Dr. Betty-Ann Henderson for her guidance with my healthcare epidemiology specialization. Thank you to the entire team at the Provincial Laboratory for Public Health in Calgary and Edmonton for their hard work in preparing the samples for this study. A special thank you to Lorraine Ingham, Nancy Yuen and their team for archiving samples, as well as Dr. Norman Neumann, Colin Reynolds and Candis Scott for preparing samples and providing insight and knowledge on the project. I would not be here today if it weren’t for Christina Ferrato, Joanne Callfas and the bacteriology team who hired me as a summer student three years ago and helped me develop a passion for clinical microbiology, so thank you for believing in me. And a particular thank you to Bryanne Rempel, who was my mentor in microbiology and life in general. iii I would especially like to thank my husband, Dylan Meyer, for his support and love while I pursued my Master’s degree. He took care of me when I forgot to take care of myself, he listened, asked questions and encouraged me throughout the entire process and I cannot thank him enough for his continued support. I would like to thank my mother and father, Jacquie and Bruce, and my brother, Nathan for always believing in me and teaching me how to believe in myself. You were all there for me when I needed encouragement and you kept me sane when I felt overwhelmed. And a special thank you to my late grandmother, Marion, for convincing all of her friends and family I was a doctor, and having them ask me for medical advice. The weird sense of confidence this gave me helped me to believe in myself more than anything else. I am incredibly thankful for my dear friends, particularly Rebecca Cooper and Kristin Roeke, for keeping me grounded when my head was in a cloud of literature reviews, and for talking me down in moments of panic. Thank you to my microbiology colleagues, in particular Erik, Alya and Rai for cheering me on and sharing in my love of microbiology. Finally, I would like to acknowledge the funders that made this project possible, in particular Alberta Agriculture and Forestry, as well as the Government of Alberta for the Queen Elizabeth II Graduate Student Scholarship, and the University of Calgary for the Eyes High Travel Award. iv Dedication I would like to dedicate this thesis to my husband, Dylan, for always encouraging and never doubting me. When I lost track of time and worked late into the evening he would have dinner ready for me, and when I was making a mountain out of a molehill he would talk me down and help me to rationalize the situation. I would also like to dedicate this thesis to my parents and grandmother for teaching me how to believe in myself and for supporting me every step of the way. v Table of Contents Abstract ............................................................................................................................... ii Acknowledgements ............................................................................................................ iii Dedication ............................................................................................................................v List of Tables .......................................................................................................................x List of Figures and Illustrations ......................................................................................... xi List of Symbols, Abbreviations and Nomenclature ...........................................................xv Epigraph ........................................................................................................................... xix CHAPTER ONE: LITERATURE REVIEW, OBJECTIVES AND INTRODUCTION TO THE PROJECT ...........................................................................................................1 1.1 Antimicrobial and antibiotics .....................................................................................2 1.1.1 Antimicrobial stewardship in Canada ...............................................................3 1.2 Resistance to antimicrobials ......................................................................................5 1.2.1 Measuring AMR ................................................................................................5 1.2.2 Impact and spread of AMR ...............................................................................6 1.2.3 Natural AMR .....................................................................................................8 1.2.4 Acquisition of resistance determinants ..............................................................9 1.2.5 Types of antimicrobials, and mechanisms of AMR ........................................12 1.2.5.1 Nucleic acid synthesis inhibitors ...........................................................14 1.2.5.2 Inhibition of cell wall synthesis .............................................................18 1.2.5.3 Inhibition of protein synthesis ...............................................................21 1.3 Resistance reservoirs ................................................................................................26 1.3.1 Resistance in humans ......................................................................................26 1.3.2 Resistance in Animals .....................................................................................29 1.3.2.1 Resistance in food animal agriculture ....................................................29 1.3.3 Resistance in crop agriculture ..........................................................................31 1.3.4 Resistance in aquaculture .................................................................................32 1.3.5 Resistance in the environment .........................................................................32 1.3.5.1 Resistance in water ............................................................................33 1.4 Groundwater and well water ..................................................................................35 1.4.1 Groundwater contamination .............................................................................36 1.4.2 Testing groundwater contamination ................................................................37 1.4.2.1 Escherichia