<i>Staphylococcus aureus</i> adapts to the host nutritional landscape to overcome tissue-specific branched-chain fatty acid requirement

Abstract

Significance Lipoylation is a posttranslational modification critical for the function of several metabolic enzymes. In the bacterial pathogen Staphylococcus aureus , lipoylation deficiency compromises growth and causes tissue-specific virulence defects. Perturbation of lipoylation causes attenuation in part due to disruption of the enzyme complex required for the synthesis of branched-chain fatty acids, an essential constituent of S. aureus membrane. S. aureus overcomes branched-chain fatty acid auxotrophy in the skin by acquiring host unsaturated fatty acids. This work underscores the adaptability of S. aureus when faced with nutrient scarcity and the relevance of lipoic acid sufficiency during infection. Our findings support the view that versatility in S. aureus membrane biogenesis must be considered when devising therapeutics.