Inflammasome-mediated glucose limitation induces antibiotic tolerance in Staphylococcus aureus

Published: 3 August 2023| Version 2 | DOI: 10.17632/6msmhr9vrs.2
Nikki Wagner, Jenna Beam, Kuan-Yi Lu, Joshua Parsons, Sarah Conlon, Brian Conlon


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.



University of North Carolina at Chapel Hill


Microbiology, Antibiotics, Inflammasome, Methicillin-Resistant Staphylococcus aureus