Jessica Petrey

Investigating Methionyl-tRNA Formyltransferase (Fmt) as a Target for Disrupting Antibiotic Persistence in Bacillus subtilis

The discovery of antibiotics has revolutionized modern medicine and remains a cornerstone of infection control. However, the efficacy of antibiotic treatment has been challenged by the ability of bacteria to survive beyond treatment, namely in the forms of resistance, tolerance, and persistence. In particular, persistence allows a subpopulation of bacterial cells (known as persisters) to withstand high dose antibiotic treatment without acquiring genetic resistance. Antibiotic persistence leads to prolonged infections and treatment, as well as facilitating the emergence of antibiotic resistant mutants. My research focuses on methionyl-tRNA formyltransferase (Fmt), an enzyme that modifies the initiator tRNA for translation initiation. While Fmt is non-essential in bacteria, it has been speculated to play roles in cellular stress responses. Interestingly, I found that disruption of the fmt gene leads to eradication of persisters by various antibiotic treatments in B. subtilis, suggesting that Fmt is critical for antibiotic persistence. By investigating how Fmt contributes to antibiotic tolerance and persistence, as well as its potential role in ribosome function under stress, I aim to uncover key mechanisms that support persisters survival against antibiotic treatment. Given its role in promoting bacterial survival, Fmt may serve as a promising target for antibiotic adjuvant therapies to enhance treatment efficacy.