Staphylococcus aureus is a metabolically flexible pathogen that causes infection in diverse settings. An array of virulence factors, including the secreted toxins, enables S. aureus to colonize different environmental niches and initiate infections by any of several discrete pathways. During these infections, both S. aureus and host cells compete with each other for nutrients and remodel their metabolism for survival. This metabolic interaction/crosstalk determines the outcome of the infection. The reprogramming of metabolic pathways in host immune cells not only generates adenosine triphosphate (ATP) to meet the cellular energy requirements during the infection process but also activates antimicrobial responses for eventual bacterial clearance, including cell death pathways. The selective pressure exerted by host immune cells leads to the emergence of bacterial mutants adapted for chronicity. These host-adapted mutants are often characterized by substantial changes in the expression of their own metabolic genes, or by mutations in genes involved in metabolism and biofilm formation. Host-adapted S. aureus can rewire or benefit from the metabolic activities of the immune cells via several mechanisms to cause persistent infection. In this review, we discuss how S. aureus activates host innate immune signaling, which results in an immune metabolic pressure that shapes S. aureus metabolic adaptation and determines the outcome of the infection.
Keywords: Staphylococcus aureus; biofilm; cell death; chronic or persistent infection; epigenetics; metabolic adaptation; metabolic reprogramming; small colony variants (SCVs); trained immunity.