Electronic Theses and Dissertations

Date

2021

Document Type

Dissertation

Degree Name

Doctor of Philosophy

Department

Biology

Committee Chair

Tit-Yee Wong

Committee Member

Carlos Estrano

Committee Member

Steven Schwartzbach

Committee Member

Lih-Yuan Deng

Abstract

The importance of maintaining a healthy microbiome is being recognized increasingly. Our research in the gut microbiome and environmental pollutants suggests that pollutants like particulate matter (PM2.5) and nanometals can induce Reactive Oxygen Species (ROS) and decrease the microbiome stability. Additionally, the abusive use of antibiotics in the past has led to great changes in the microbiome and caused the rise of many antibiotic-resistant strains.Developing a new antibiotic is costly and time-consuming. Methods to improve the existing drugs should be cost-effective. A narrow-spectrum antibiotic that targets only the problematic pathogens should prevent microbiome disruption and reduce the rise of antibiotic resistance. This requires understanding the physiology of microbes growing in their specific environment. However, little is known on how environment affect the bacterias response to the antibiotics.I initiated a project to understand the triangulation between bacteria, their growth environments, and their responses to different classes of antibiotics. I noticed that triclosan (TCS), a xenobiotic found in many household products, can often interfere with an antibiotic. I used 16 different bacterial strains and 6 different classes of antibiotics to study the interaction between TCS-antibiotic on a bacterium. TCS could act synergistically or antagonistically with antibiotics. Studies on the antagonistic interaction suggest that TCS can induce a multidrug efflux pump making the bacteria more resistant to certain antibiotics. This discovery also explains a long mystery of the so-called paradoxical effect (also called the Eagles Effect) where some strains of bacteria which could not survive low concentrations of antibiotics would survive at higher concentrations.Using Azotobacter vinelandii, a nitrogen-fixing, obligate aerobic bacteria as a model organism, I demonstrated that interaction of other environmental factors could change the sensitivity/resistance to a certain antibiotic. The complex interactions between antibiotic-environmental factors can be partially resolved by using a full-factorial design. We also proved that oxidative stress as a common mechanism of bacterial cell death theory does not hold for all antibiotics. Our proof-of-concept model suggests that it is possible to enhance the efficacy of preexisting antibiotic by manipulating various environmental factors. This should provide a cost-effective approach towards personalized medicine as well.

Comments

Data is provided by the student.

Library Comment

Dissertation or thesis originally submitted to ProQuest

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