Date of Award

Summer 2026

Language

English

Embargo Period

7-27-2026

Document Type

Master's Thesis

Degree Name

Master of Science (MS)

College/School/Department

Department of Biomedical Sciences

Program

Biomedical Sciences

First Advisor

Dr. Sian Owen

Committee Members

Dr. Jon Paczkowski, Dr. Keith Derbyshire

Keywords

Plasmid-dependent Bacteriophages, Conjugation, Antibiotic Resistance

Subject Categories

Life Sciences | Medical Sciences | Medicine and Health Sciences | Microbiology | Public Health

Abstract

The alarming rise of carbapenem-resistant bacteria poses an urgent global health threat, driven in large part by the horizontal spread of carbapenemase-encoding plasmids (Ma et al., 2023). These plasmids are often highly mobile and transmissible, enabling rapid dissemination of resistance genes across diverse bacterial populations. Their mobility is largely mediated by conjugation, a process dependent on the formation of pili, which serve as physical bridges for plasmid transfer between cells (Murray et al. 2022; San Millan and MacLean 2017; Virolle et al. 2020). Beyond their role in gene exchange, these pili also act as entry points for a unique class of viruses known as plasmid-dependent bacteriophages (PDPs), which specifically target bacteria expressing conjugative pili (Colom et al., 2019; Penttinen et al., 2021).

Traditional antibiotic strategies have proven ineffective at curbing the spread of such plasmids, highlighting the need for novel, targeted interventions (Ma et al., 2023). One promising avenue is the exploitation of PDPs to selectively attack plasmid-carrying, drug-resistant bacteria. However, effective implementation of this strategy requires a deeper understanding of the genetic and regulatory mechanisms controlling pilus expression and plasmid transfer, especially in clinically relevant carbapenemase plasmids, which often exhibit low or variable conjugation efficiencies (Colom et al., 2019; Hardiman et al., 2016; Jalasvuori et al., 2011; Ojala et al., 2013).

This thesis aims to address these gaps by engineering or evolving hyper-conjugative plasmid variants with enhanced pilus production. These modified strains will serve as tools to isolate novel plasmid-dependent phages from environmental samples. In addition, this work seeks to develop fluorescent labeling strategies to visualize phage–pilus interactions, providing new insight into the mechanisms of phage adsorption and infection of conjugative pili. In doing so, the project will uncover genetic barriers to conjugation, identify regulatory elements that control pilus expression, and characterize the interactions between phages and their bacterial hosts.

Collectively, these studies will provide foundational insights into the biology of conjugative plasmids and their exploitation by phages, while establishing a platform for the development of phage-based precision antimicrobials designed to destabilize and ultimately eliminate plasmid-borne carbapenem resistance in bacterial populations.

License

This work is licensed under the University at Albany Standard Author Agreement.

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