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Publication Date

2022-05-09

First Advisor

Robert L. Dorit

Document Type

Honors Project

Degree Name

Bachelor of Arts

Department

Biochemistry

Keywords

bacteriocin, colicin, antibiotic, antibiotic resistance, narrow-spectrum, antimicrobial, genotype-phenotype, cost of resistance, fitness cost, cross-resistance

Abstract

While the development of antibiotic therapies has drastically improved the treatment and outcomes of bacterial infections, their utility in the clinic is now severely curtailed by the emergence and prevalence of antibiotic resistance. There are nearly 3 million antibiotic-resistant infections per year in the US alone, leading to 35,000+ deaths and billions in additional healthcare costs (CDC, 2019). In response to the growing threat of antibiotic resistance, the development of targeted, narrow-spectrum antimicrobials is emerging as an increasingly attractive alternative to conventional broad-spectrum antibiotics. This thesis explores one class of narrow-spectrum antibiotic: the bacteriocins. Bacteriocins are a heterogenous class of ribosomally-synthesized proteins produced by most bacteria to target and kill other conspecific or closely-related bacteria. Specifically, we focus on colicins, bacteriocins produced by E. coli, as a model system. In this study, we set out to: 1) select for resistance in solid and liquid media; 2) infer the molecular basis of different resistance mechanisms through the analysis of cross-resistance profiles; 3) measure the fitness costs associated with resistance; and 4) confirm the molecular basis of different resistance mechanisms through whole-genome sequencing. We were able to select for resistance in both solid and liquid and media, infer possible mechanisms of resistance from the cross-resistance profiles observed, quantitate some of the fitness costs associated with resistance, and begin whole-genome sequencing of samples. This data helps characterize the phenotypic profiles associated with resistance to various colicins, and prepare for future work linking these profiles to the underlying genotypes and mechanisms of resistance.

Rights

©2022 Helen Wang. Access limited to the Smith College community and other researchers while on campus. Smith College community members also may access from off-campus using a Smith College log-in. Other off-campus researchers may request a copy through Interlibrary Loan for personal use.

Language

English

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