Synthesis of perfluorooctanoic acid-containing membrane lipids by human pathobionts

Per- and polyfluoroalkyl substances (PFAS) are synthetic fluorinated compounds used widely in industrial and consumer products. They are unusually stable due to carbon-fluorine bonds and resistant to degradation, making them persistent contaminants in water, soil, and biota. PFAS are associated with adverse health effects in humans including cancer and liver disease. The effects of PFAS on human-associated bacteria are largely unexplored, a significant gap in knowledge because these bacteria are exposed to PFAS in vivo at sites including the colon and bladder. One of the best studied PFAS compounds is perfluorooctanoic acid (PFOA), an eight-carbon perfluorinated carboxylic acid whose structure is analogous to a fatty acid. Here, we cultured Enterococcus faecalis, a Gram-positive bacterium, and Pseudomonas aeruginosa, a Gram-negative bacterium, in growth medium supplemented with PFOA and corresponding control conditions and performed lipidomic analyses using liquid chromatography-tandem mass spectrometry (LC-MS/MS) to elucidate lipid remodeling in response to PFOA exposure. Strikingly, novel fluoroalkyl-containing membrane lipids are synthesized by both of these bacteria, with each species synthesizing unique fluoroalkyl-lipids. Moreover, a high-level daptomycin-resistant strain of E. faecalis produces strikingly high levels of fluoroalkyl-lipids, demonstrating that prior antibiotic exposure and concomitant effects on bacterial evolution can alter bacterial interactions with PFAS. Because bacterial lipids are important immunomodulators in vivo, we propose that PFAS-containing bacterial lipids may be novel mediators of host-microbe-pollutant interactions. Our results also establish a novel mechanism for the bioaccumulation of PFOA and, potentially, for bioremediation of PFOA in biological systems such as the human gastrointestinal tract.