Date of Award

2017

Degree Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Graduate Group

Cell & Molecular Biology

First Advisor

Elizabeth A. Grice

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 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.

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