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Thesis Format

Monograph

Degree

Master of Science

Program

Microbiology and Immunology

Supervisor

Dr. Michael J Fruci

Affiliation

Agriculture and Agri-Food Canada

2nd Supervisor

Dr. Martin J McGavin

Abstract

Asulam is an herbicide that is structurally analogous to sulfonamide antibiotics (sulfas), with the potential to contribute to the global antibiotic resistance crisis by cross-selecting for sulfa-resistant bacteria. To determine if asulam can select for antibiotic resistant bacteria, isothermal titration calorimetry (ITC) was used to assess the binding affinity of asulam with the target protein of sulfas, dihydropteroate synthase (DHPS). ITC confirmed asulam interacts with DHPS, and in vitro directed evolution experiments showed that prolonged asulam exposure can select for sulfa-insensitive DHPS in E. coli. Since mobile sul genes also encode for sulfa-insensitive DHPS, the potential effect of asulam on the dissemination of the sul genes in a simulated bacterial community was assessed. These data suggested that asulam can promote sulfa-resistance by increasing the frequency of chromosomal folP mutations, and/or acquisition of sul genes in E. coli, and uniquely induce deletions of multiple genes at concentrations exceeding environmental relevance.

Summary for Lay Audience

Antibiotic resistant bacteria cause infections that do not respond to standard treatments and require more costly and intensive interventions. These types of infections have become increasingly common and reducing the prevalence of antibiotic resistance has become a healthcare priority. An effective strategy has been the reduction of usage of antibiotics, as the misuse and overuse of these drugs is known to contribute to the increased prevalence of these infections. However, other chemicals can also increase the frequency of antibiotic resistance in bacterial communities, including agrichemicals such as pesticides and herbicides. When bacteria that reside in crop soil are exposed to these agrichemicals, they can become resistant to antibiotics and have the potential to spread to humans via consumptions of food grown in contaminated soil. Therefore, determining how agrichemicals contribute to promoting antibiotic resistance to implement appropriate regulations regarding the usage of these chemicals is paramount for reducing the burden of antibiotic resistant bacterial infections on the healthcare system. In this study, the herbicide asulam is assessed for its ability to select for and promote the dissemination of sulfonamide antibiotic resistant bacteria due to the chemical similarities shared between this herbicide and this class of antibiotics.

Creative Commons License

Creative Commons Attribution 4.0 License
This work is licensed under a Creative Commons Attribution 4.0 License.

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