Host-derived long-chain fatty acids are key players at the host-pathogen interface. Some bacteria (e.g.: Vibrio cholerae) are very apt at provoking the release of these FAs by host cells to promote pathogen growth. Contrastingly, deficits in sapienic acid, an antimicrobial FA exclusively found on the human skin, have been linked to increased colonization with S. aureus in patients with skin disorders such as atopic dermatitis. We are investigating the antibacterial mode of action of FAs. Given the ubiquitous nature of FAs in various host environments, there is a wealth of bacterial adaptation strategies to FAs. Deciphering how bacteria survive in FA-rich host environments may pave the way for a rational design of FA-based combination therapies with classical antibiotics.