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Spatiotemporal Dynamics of Collective Antibiotic Resistance in an Opportunistic Pathogen
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| 자료유형 | 학위논문 |
|---|---|
| 서명/저자사항 | Spatiotemporal Dynamics of Collective Antibiotic Resistance in an Opportunistic Pathogen. |
| 개인저자 | Hallinen, Kelsey. |
| 단체저자명 | University of Michigan. Biophysics. |
| 발행사항 | [S.l.]: University of Michigan., 2019. |
| 발행사항 | Ann Arbor: ProQuest Dissertations & Theses, 2019. |
| 형태사항 | 127 p. |
| 기본자료 저록 | Dissertations Abstracts International 81-05B. Dissertation Abstract International |
| ISBN | 9781687929495 |
| 학위논문주기 | Thesis (Ph.D.)--University of Michigan, 2019. |
| 일반주기 |
Source: Dissertations Abstracts International, Volume: 81-05, Section: B.
Advisor: Wood, Kevin. |
| 이용제한사항 | This item must not be sold to any third party vendors.This item must not be added to any third party search indexes. |
| 요약 | Antibiotic resistance is a critical obstacle that threatens our ability to successfully treat bacterial infections. While a great deal is known about the molecular mechanisms that underlie resistance, much less is known about how these localized molecular events contribute to dynamics and evolution at the scale of the microbial community. In this work, I combine quantitative laboratory experiments on bacterial communities with mathematical modeling to investigate the effects of antibiotic exposure on populations of E. faecalis, an opportunistic human pathogen, across multiple length scales. In spatially-extended, surface associated communities (biofilms), I find that subinhibitory concentrations of lysis-inducing antibiotics can promote biofilm formation, a counterintuitive phenomenon driven by an interplay between inhibitory effects of antibiotics and drug-induced cell lysis, which enhances biofilm formation through the release of extracellular DNA (eDNA). As drug concentration is increased to inhibitory levels, biofilms are characterized by micron-scale spatial organization, with drug-sensitive ancestral cells surrounded by protective sub-populations of enzyme-producing resistant cells. This cooperative resistance- where genetically resistant cells promote survival of neighboring drug-sensitive cells- leads to rich dynamical behavior on longer length scales. Specifically, in planktonic populations of sensitive and resistant cells, we observe bistability between population survival and extinction, quasi-stable co-existence at otherwise inhibitory drug concentrations, and damped oscillations due to ecological feedback between the population and the environment. Furthermore, I show that temporally varying dosing regimens can be used to minimize population size without requiring more total drug. My results highlight the important roles of intercellular cooperation, spatial heterogeneity, and environmental dynamics in shaping the growth and evolution of microbial communities exposed to antibiotics. |
| 일반주제명 | Biophysics. Microbiology. |
| 언어 | 영어 |
| 바로가기 | 
: 이 자료의 원문은 한국교육학술정보원에서 제공합니다. |
