University of Pennsylvania ScholarlyCommons Publicly Accessible Penn Dissertations 2017 Impact Of Topical Antimicrobial Treatments On Skin Bacterial Communities Adam Sanmiguel University of Pennsylvania, [email protected] Follow this and additional works at: https://repository.upenn.edu/edissertations Part of the Bioinformatics Commons, and the Microbiology Commons Recommended Citation Sanmiguel, Adam, "Impact Of Topical Antimicrobial Treatments On Skin Bacterial Communities" (2017). Publicly Accessible Penn Dissertations. 2567. https://repository.upenn.edu/edissertations/2567 This paper is posted at ScholarlyCommons. https://repository.upenn.edu/edissertations/2567 For more information, please contact [email protected]. Impact Of Topical Antimicrobial Treatments On Skin Bacterial Communities Abstract Skin is our primary interface to the outside world, representing a diverse habitat with a multitude of folds, invaginations, and appendages. While each of these structures is essential to host cutaneous function, they also serve as unique ecological niches that can support an array of microbial inhabitants. Together, these microorganisms constitute the skin microbiome, an assemblage of bacteria, fungi, and viruses with the potential to influence cutaneous biology. While a number of studies have described the importance of these residents to immune function and development, none to date have assessed their dynamics in response to antimicrobial stress, nor the impact of these perturbations on host cutaneous defense. Rather the majority of work in this regard has focused on a subset of microorganisms studied in isolation. Herein, we present the impact of topical antibiotics and antiseptics on skin bacterial communities, and describe their potential to shape cutaneous interactions. Using mice as a model system, we show that antibiotics can elicit a distinct shift in skin inhabitants characterized by decreases in diversity and domination by previously minor contributors. By contrast, we report a relatively modest impact of antiseptics on skin bacteria, largely preserving inhabitant structure at the community-level. Despite these differences, we show a significant decrease in Staphylococcus residents regardless of treatment, a subset of inhabitants which we also found to influence colonization yb the skin pathogen Staphylococcus aureus. To determine the relevance of these findings in human systems, we further treated thirteen subjects with antiseptics at the forearm and back. Similar to mouse experiments, we observed a relatively minor effect of these treatments on bacterial inhabitants at the population-level. However, when controlling for factors such as interindividual differences and body-site specificity, we observed a more significant impact, governed in large part by decreases in lowly abundant members of the skin microbiota. We also found bacterial identity to be a key contributor to this effect, with certain skin taxa exhibiting more robust shifts than others. In all, these results underscore the ability of antimicrobial drugs to alter skin bacterial residence, and outline the importance of these inhabitants to host cutaneous defense. Degree Type Dissertation Degree Name Doctor of Philosophy (PhD) Graduate Group Cell & Molecular Biology First Advisor Elizabeth A. Grice Keywords Antibiotic, Antiseptic, Bacteria, Microbiome, Sequencing, Skin Subject Categories Bioinformatics | Microbiology This dissertation is available at ScholarlyCommons: https://repository.upenn.edu/edissertations/2567 IMPACT OF TOPICAL ANTIMICROBIAL TREATMENTS ON SKIN BACTERIAL COMMUNITIES Adam Jason SanMiguel A DISSERTATION in Cell and Molecular Biology Presented to the Faculties of the University of Pennsylvania in Partial Fulfillment of the Requirements for the Degree of Doctor of Philosophy 2017 Supervisor of Dissertation Graduate Group Chairperson ____ ____________________________ ____ _____________________________ Elizabeth A. Grice Ph.D. Daniel S. Kessler, Ph.D. Assistant Professor in Dermatology Associate Professor of Cell and Developmental Biology Dissertation Committee Frederic D. Bushman, Ph.D. Ronald G. Collman, M.D. William M. Measey Professor in Microbiology Professor of Medicine Mark Goulian, Ph.D. Sarah A. Tishkoff, Ph.D. Professor of Biology David and Lyn Silfen University Professor IMPACT OF TOPICAL ANTIMICROBIAL TREATMENTS ON SKIN BACTERIAL COMMUNITIES COPYRIGHT 2017 Adam Jason SanMiguel This work is licensed under the Creative Commons Attribution- NonCommercial-ShareAlike 3.0 License To view a copy of this license, visit https://creativecommons.org/licenses/by-nc-sa/3.0/us/ DEDICATION To my mentor Elizabeth Grice and the other members of Club Grice, who have contributed greatly to my successes and helped me to overcome my far more frequent encounters with failure. iii ACKNOWLEDGEMENT I am extremely grateful to everyone who has helped me over the past few years to develop as both a scientist and a person. Within the laboratory, my advisor Elizabeth Grice has been instrumental to my accomplishments. I feel incredibly fortunate to have learned from such a kind and passionate mentor, who has always pushed me to think critically and work harder to answer difficult questions. I am also thankful for the support I have received from my fellow lab members, including the old guard of Amanda Tyldsley, Geoffrey Hannigan, Brendan Hodkinson, and Jacquelyn Meisel, as well as the “newer” members, Casey BM, Joseph Horwinski, Lindsay Kalan, Michael Loesche, and Qi Zheng. I would also like to thank my thesis committee of Rick Bushman, Ron Collman, Mark Goulian, and Sarah Tishkoff. Their comments often sparked new and exciting directions in my research. I appreciate their willingness to invest their time in my growth and development, and I am certain my project would not be what it is today without their guidance and support. In a similar manner, I would also like to thank the Dermatology Department for their assistance over the years. Their insights and feedback helped me to refine my hypotheses and develop a number of new avenues in my research. Finally, I would like to acknowledge my friends and family for their support. Without my wife Jennifer, graduate school would have been immensely more difficult. She has always been there to help me in my times of need, and for this I am iv extremely thankful. Although my family will still claim they do not quite understand what it is I do, they have always taken an interest in my studies and humored me with questions about my research. I, of course, would not be here without them, and for this they deserve the greatest amount of gratitude. v ABSTRACT IMPACT OF TOPICAL ANTIMICROBIAL TREATMENTS ON SKIN BACTERIAL COMMUNITIES Adam Jason SanMiguel Elizabeth Anne Grice, Ph.D. Skin is our primary interface to the outside world, representing a diverse habitat with a multitude of folds, invaginations, and appendages. While each of these structures is essential to host cutaneous function, they also serve as unique ecological niches that can support an array of microbial inhabitants. Together, these microorganisms constitute the skin microbiome, an assemblage of bacteria, fungi, and viruses with the potential to influence cutaneous biology. While a number of studies have described the importance of these residents to immune function and development, none to date have assessed their dynamics in response to antimicrobial stress, nor the impact of these perturbations on host cutaneous defense. Rather the majority of work in this regard has focused on a subset of microorganisms studied in isolation. Herein, we present the impact of topical antibiotics and antiseptics on skin bacterial communities, and describe their potential to shape cutaneous interactions. Using mice as a model system, we show that antibiotics can elicit a distinct shift in skin inhabitants characterized by decreases in diversity and domination by previously minor contributors. By vi contrast, we report a relatively modest impact of antiseptics on skin bacteria, largely preserving inhabitant structure at the community-level. Despite these differences, we show a significant decrease in Staphylococcus residents regardless of treatment, a subset of inhabitants which we also found to influence colonization by the skin pathogen Staphylococcus aureus . To determine the relevance of these findings in human systems, we further treated thirteen subjects with antiseptics at the forearm and back. Similar to mouse experiments, we observed a relatively minor effect of these treatments on bacterial inhabitants at the population-level. However, when controlling for factors such as interindividual differences and body-site specificity, we observed a more significant impact, governed in large part by decreases in lowly abundant members of the skin microbiota. We also found bacterial identity to be a key contributor to this effect, with certain skin taxa exhibiting more robust shifts than others. In all, these results underscore the ability of antimicrobial drugs to alter skin bacterial residence, and outline the importance of these inhabitants to host cutaneous defense. vii TABLE OF CONTENTS LIST OF FIGURES..............................................................................................xii LIST OF TABLES...............................................................................................xiv CHAPTER 1 Introduction.................................................................................1 1.1 Historical perspective.......................................................................................................................1