Host nutrient milieu drives an essential role for aspartate biosynthesis during invasive <i>Staphylococcus aureus</i> infection
Aimee D. Potter, Casey E. Butrico, Caleb A. Ford, Jacob M. Curry, Irina Trenary, Srivarun S. Tummarakota, Andrew S. Hendrix, Jamey D. Young, James E. Cassat
Abstract
Significance Staphylococcus aureus can infect a diverse array of host environments. The broad tissue tropism of S. aureus requires metabolic flexibility to utilize the variety of nutrient sources found within target organ systems. In this work, we conducted a systematic analysis of the central metabolic pathways required for S. aureus survival during bone infection, one of the most frequent sites of invasive staphylococcal disease. We show that S. aureus requires aspartate biosynthesis to survive during bone infection, despite possessing an aspartate transporter, due to inhibition of aspartate utilization by the amino acid glutamate. Our results reveal a crucial role for inflammation-associated shifts in the host nutrient milieu for determining the metabolic pathways utilized by S. aureus during invasive infection.