Inflammasome-mediated glucose limitation induces antibiotic tolerance in Staphylococcus aureus

Interactions with the host immune system alters S. aureus response to therapeutic antibiotics. We find that S. aureus α-toxin, a pore-forming toxin, interacts with macrophages to alter the microenvironment of the pathogen and influence its susceptibility to antibiotics. α-toxin-mediated activation of the NLRP3 inflammasome induces antibiotic tolerance through increased glycolysis in the host cells, resulting in glucose limitation and ATP depletion in S. aureus. Additionally, inhibition of NLRP3 activation improves antibiotic efficacy in vitro and in vivo. Our findings identify interactions between S. aureus and the host that result in metabolic crosstalk that can determine the outcome of antimicrobial therapy. This data contains GraphPad Prism files containing data from the main and supplemental figures of J.E.Beam. et al., 2023.