| First Author | Beam JE | Year | 2023 |
| Journal | iScience | Volume | 26 |
| Issue | 10 | Pages | 107942 |
| PubMed ID | 37790275 | Mgi Jnum | J:355284 |
| Mgi Id | MGI:7538578 | Doi | 10.1016/j.isci.2023.107942 |
| Citation | Beam JE, et al. (2023) Inflammasome-mediated glucose limitation induces antibiotic tolerance in Staphylococcus aureus. iScience 26(10):107942 |
| abstractText | Staphylococcus aureus is a leading human pathogen that frequently causes relapsing infections. The failure of antibiotics to eradicate infection contributes to infection relapse. Host-pathogen interactions have a substantial impact on antibiotic susceptibility and the formation of antibiotic tolerant cells. In this study, we interrogate how a major S. aureus virulence factor, alpha-toxin, interacts with macrophages to alter the microenvironment of the pathogen, thereby influencing its susceptibility to antibiotics. We find alpha-toxin-mediated activation of the NLRP3 inflammasome induces antibiotic tolerance. Induction of tolerance is driven by 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, suggesting that this strategy has potential as a host-directed therapeutic to improve outcomes. Our findings identify interactions between S. aureus and the host that result in metabolic crosstalk that can determine the outcome of antimicrobial therapy. |
