(Georgia Institute of Technology, 2021-12-14)
Selvakumar, Hemaa
When single-celled prokaryotic organisms, one of the simplest forms of life, develop the ability to exhibit complex emergent properties such as social cooperation, resource capture, and enhanced survivability, the individual limitations of existence can be overcome which would otherwise be unlikely. Emergent properties of biofilms such as matrix production, quorum sensing, and coordinated lifecycle offers structural and functional
advantages which makes them highly successful at evading destruction by antimicrobials and immune defenses. With few, if any, novel antibiotics in the clinical pipeline, there is a resurgence of interest in alternatives such as phage therapy, the practice of bacterial viruses known as bacteriophages that infect and lyse bacteria to treat infections. In this thesis, we explore the understudied impact of phage titer on biofilm dynamics and outcomes. We determined that the biofilm developmental stage at the time of phage addition modulates its response. These responses vary as a function of the phage dose and can be broadly organized into four distinct classes. In each of these classes, we observe that high phage doses restrain the biofilm from transitioning into the next stage of their developmental cycle. A paradoxical aspect of this result is that mature biofilms exposed to high phage titers are enhanced by phage treatment. Despite this apparently unwanted outcome, the
inhibition of biofilm dispersion in phage-treated samples could potentially minimize the further spread of infections to other locations. These results comprehensively demonstrate
predictable biofilm outcomes versus phage dosage and biofilm age, and will provide guidance in advancing phage-based personalized medicine when generalized treatments fail. Collectively, this dissertation derives insights on the advantages and limitations of phages to inhibit, control, and eliminate biofilms.