Date of Award

2015

Degree Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Graduate Group

Cell & Molecular Biology

First Advisor

Elizabeth A. Grice

Abstract

Human skin is colonized by diverse microbial communities that have broad impacts on health and disease. Bacterial communities have been associated with dermatological diseases including Atopic Dermatitis and Psoriasis, and while roles of virus communities (viromes) in cutaneous health are poorly characterized, virome dysbiosis has been implicated in other human diseases and individual viruses are known to impact cutaneous health. Here we present a comprehensive research program aimed at broadly understanding the roles of bacteria and viruses in human dermatological health and perturbation by wounding. In the first section, we characterize the healthy human skin virome and investigate potential interactions between virus and bacterial communities. Samples were collected from sixteen subjects at eight body sites over one month. Virome diversity and composition varied by natural skin occlusion and the microenvironment substrates. Viruses were enriched for temperate replication-cycle genes, and maintained genes encoding potential antibiotic resistance and virulence factors. We also highlighted potential interactions between the virus (phage) and bacterial communities, including CRISPR targeting and significant ecological associations by co-occurrence modeling. This work provides a greater ecological context for our individualized understanding of cutaneous viruses, and provides a foundation for future studies of the skin virome upon perturbation and disease. In the second section, we characterize the microbial communities associated with skin perturbation in the form of acute, open fracture wounding. Thirty subjects presenting to the Hospital of the University of Pennsylvania for acute care of open fractures were enrolled in a prospective cohort study. Microbiota were collected from wound center and adjacent skin upon presentation to the ER and during follow up visits. Bacterial communities were studied using 16S rRNA amplicon sequencing. Microbiome composition and diversity colonizing open fracture wounds became increasingly similar to adjacent skin microbiota with healing. Clinical factors were associated with various aspects of microbiota diversity and composition. We also developed an analysis tool patPRO to facilitate analysis of this longitudinal dataset, and to aid others in analyses of similar data. The results of this pilot study demonstrate the diversity and dynamism of the open fracture microbiota, and their relationship to clinical variables.

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