Metabolic responses to Staphylococcus aureus airway infection

Respiratory tract infections caused by antibiotic-resistant Staphylococcus aureus are often fatal and largely influenced by the pathogen's ability to overcome host immune defenses. Despite the importance of immune evasion, staphylococci, along with their exoproducts, are also known to modulate specific metabolic pathways within the respiratory epithelium and infection hot spot-infiltrating phagocytic cells, thereby impacting inflammatory and antimicrobial responses. Here, we briefly discuss how Staphylococcus aureus induces disease-related metabolic alterations in professional and nonprofessional phagocytes during acute and chronic infections of the lung. Specifically, we focus on metabolic plasticity of airway epithelial cells and predominant phagocytes upon sensing of S. aureus and further detail metabolic adaptation strategies of staphylococcal small colony variants that often cause persistent and hard-to-treat infections within the airways of individuals suffering from cystic fibrosis. In this context, we highlight how metabolic rerouting and buildup of specific bacterial metabolites, including intermediates of the tricarboxylic acid cycle, can shift the lifestyle of S. aureus toward sessility and intracellular persistence. Coupled with a section addressing the role of bacterial energy metabolism during S. aureus respiratory infections, these insights may aid in the design of novel anti-infective and immunometabolism-based therapeutic strategies.