Document Type
Thesis
Date of Degree Completion
Spring 2026
Degree Name
Master of Science (MS)
Department
Biology
Committee Chair
Gabrielle A. Stryker
Second Committee Member
Jill H. Zeilstra-Ryalls
Third Committee Member
Blaise Dondji
Abstract
Per- and polyfluoroalkyl substances (PFAS) are synthetic compounds widely used in industrial and consumer applications due to their exceptional chemical stability conferred by strong carbon–fluorine bonds. However, this stability also drives environmental persistence and bioaccumulation, and the molecular mechanisms underlying PFAS toxicity remain poorly understood. In this study, we used a genetic approach to investigate PFAS toxicity in Salmonella enterica serovar Typhimurium TA1535 (Ames strain). Six independent PFAS-tolerant mutants (DL1–DL6) were isolated based on their ability to grow within zones of inhibition produced by perfluorooctanoic acid (PFOA). These mutants exhibited distinct, condition-dependent tolerance profiles to both PFOA and GenX™, a shorter-chain alternative to PFOA. Whole-genome sequencing identified multiple non-synonymous mutations across functionally diverse genes, including those involved in transcriptional regulation and membrane-associated processes. Targeted gene knockouts demonstrated that disruption of specific loci, including yfhM (α2macroglobulin), vapBC (toxin–antitoxin system), yhaJ (LysR-type regulator), and a putative membrane protein (STM4464), significantly altered bacterial growth in the presence of PFAS. Notably, these phenotypic differences were observed in the presence of fluorinated compounds (PFOA and GenX™) but not in the presence of octanoic acid (OA), a non-fluorinated structural analog, indicating that PFAS toxicity is driven by fluorination rather than by carbon chain length alone. Together, these findings support a model in which PFAS toxicity operates through the disruption of multiple cellular systems, with tolerance arising from the combined effects of diverse genetic adaptations rather than a single resistance mechanism. This work provides mechanistic insight into PFAS interactions with bacteria and establishes a framework for identifying molecular targets of PFAS toxicity.
Recommended Citation
Lakshminarayanan, Dharshana; Castro-Murcia, Cindy Y.; Zeilstra-Ryalls, Jill H.; Ranson Olson, Britton; and Stryker, Gabrielle A., "Genetic Analysis of Salmonella Enterica Tolerance to Per- and Polyfluoroalkyl Substances" (2026). All Master's Theses. 2373.
https://digitalcommons.cwu.edu/etd/2373