Fatty acids, carboxylic acids with a saturated or unsaturated aliphatic chain, are classified as short- (<6 carbons), medium- (6–10 carbons), and long-chain fatty acids (LCFAs) (≥12 carbons) depending upon their chain length [1]. Bacteria acquire LCFAs from their host where they are present as principal components of membrane lipids, part of storage lipids (lipid droplets [LD]), triacylglycerols on the skin and nasal lining, in lung surfactants, and in the lining of the gastrointestinal tract 2, 3, 4, 5, 6••, 7•, 8. Free LCFAs can be released from the host by the action of lipases and can also be obtained in the gut from the degradation of triglycerides found in dietary fats 6••, 8, 9, 10. Depending on their fate inside the bacterial cell, that is, a source of metabolic energy, incorporation into the membrane, or recognition as signaling molecules, LCFAs may be beneficial or detrimental to bacteria. Multiple reviews have discussed the antimicrobial, antivirulence, and antibiofilm roles of LCFAs in bacteria, principally due to their fate as signaling molecules or their incorporation into the membrane 7•, 11•, 12•, 13•, 14, 15. Although the use of LCFAs as nutrients also impacts the survival and virulence of bacteria, this area of research has not been comprehensively reviewed. Moreover, in recent years, LCFA degradation has been associated with stress, in particular, in the laboratory strain of the Gram-negative bacterium Escherichia coli (E. coli K-12) 16••, 17•, 18•, 19••, 20. The emerging importance of LCFAs as nutrients during infection by Gram-negative pathogens makes it imperative to understand whether these bacteria are also predisposed to stress and if so, what are their preventive or combat strategies.

In this review, following a brief overview of the LCFA degradation pathway in Gram-negative bacteria, we provide up-to-date information on the role of LCFAs as nutrients in the proliferation and virulence of Gram-negative human pathogens and summarize the known association of LCFA metabolism with stress in E. coli. We identify knowledge gaps that need to be filled to strengthen the significance of LCFA utilization and its integration with other cellular processes in mediating host–bacterial interactions.