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Inflammatory Glucose Restriction in Liver Induces Antibiotic Resistance to

Shoji Inaja

Staphylococcus aureus is a major human pathogen that often causes recurrent infections. Host-pathogen interactions have been shown to have a profound effect on antibiotic sensitivity and the formation of antibiotic-resistant cells. This study investigates α toxin, an important. S. aureus virulence factor, interacts with macrophages to alter the pathogen’s microenvironment, thereby affecting its susceptibility to antibiotics. We found that atoxin-mediated activation of the NLRP3 inflammasome induces antibiotic resistance in the cytoplasm of host cells. Induction of antibiotic resistance is promoted by increased glycolysis in host cells, leading to glucose restriction and ATP depletion in S.aureus.In addition, inhibition of NLRP3 activation improves the efficacy of antibiotics in vitro and in vivo.Our results identify interactions between the host and S.aureus that result in metabolic crosstalk that can determine the outcome of antibacterial therapy.