Date of Completion
Dr. Wendy Mok, Dr. Patricia Rossi
Molecular and Cell Biology
Bacteria | Bacterial Infections and Mycoses | Biochemistry | Biology | Chemicals and Drugs | Infectious Disease | Medical Microbiology | Microbiology | Molecular Biology | Molecular Genetics | Pathogenic Microbiology
Antibiotic treatment failure is a public health crisis, with a 2019 report stating that roughly 35,000 deaths occur in the United States yearly due to bacterial infections that are unresponsive to antibiotics (1). One complication in the treatment of bacterial infection is antibiotic persistence which further compromises our battle to effectively treat infection. Bacterial persisters can exist in clonal bacterial cultures and can tolerate antibiotic treatment by undergoing reversible phenotypic changes. They can survive drug concentrations that their genetically identical kin cannot. Some persisters remain in a slow growing state and are difficult to target with current antibiotics. A specific class of antibiotics that act as DNA topoisomerase inhibitors, fluoroquinolones (FQ), can target non-growing Escherichia coli that are often tolerant of other on-the-market antibiotics. We focus on two FQ drugs, Levofloxacin (Levo) and Delafloxacin (Dela), both of which were shown to reduce survival in wildtype E. coli cultures when treated alongside glucose (2). Analysis to elucidate this phenomenon shows that during Levo treatment, glucose stimulates transcriptional events, rendering experimental cultures more vulnerable to DNA damage. This was not observed with Dela treatment, leaving a gap in understanding the full impact of glucose potentiation on FQ’s. It has been previously shown that persistence of antibiotic-treated E. coli can instead depend on the timing of induction of SOS responses that are needed to repair DNA damage (3). Through gaining a better understanding of the timing of repair mechanisms in wildtype E. coli and the impact that glucose potentiated Levo and Dela have on this, we may more efficiently target and prevent antibiotic treatment failure.
Schofield, Stephanie, "Elucidating the Impact of SOS-response Timing in on Escherichia coli Survival Following Treatment with Fluoroquinolone Topoisomerase Inhibitors" (2023). Honors Scholar Theses. 971.