Fatty Acids Regulate Stress Resistance and Virulence Factor Production for Listeria monocytogenes

Fatty acids (FAs) are the major structural component of cellular membranes, which provide a physical and chemical barrier that insulates intracellular reactions from environmental fluctuations. The native composition of membrane FAs establishes the to-pological and chemical parameters for membrane-associated functions and is therefore modulated diligently by microorganisms especially in response to environmental stresses. However, the consequences of altered FA composition during host-pathogen interactions are poorly understood. The food-borne pathogen Listeria monocytogenes contains mostly saturated branched-chain FAs (BCFAs), which support growth at low pH and low temperature. In this study, we show that anteiso-BCFAs enhance bacte-rial resistance against phagosomal killing in macrophages. Specifically, BCFAs protect against antimicrobial peptides and pepti-doglycan hydrolases, two classes of phagosome antimicrobial defense mechanisms. In addition, the production of the critical virulence factor, listeriolysin O, was compromised by FAmodulation, suggesting that FAs play a key role in virulence regulation. In summary, our results emphasize the significance of FAmetabolism, not only in bacterial virulence regulation but also in membrane barrier function by providing resistance against host antimicrobial stress. Biological functions that modulate the growth and virulence ofpathogenic organisms, such as toxin secretion or nutrient ac-quisition, involve cellular membranes, which are composed pri-marily of phospholipids. For example, inVibrio cholerae, exposure to surface-disrupting bile leads to rapid alterations in membran