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Inflammasome-mediated glucose limitation induces antibiotic tolerance in Staphylococcus aureus.

Publication ,  Journal Article
Beam, JE; Wagner, NJ; Lu, K-Y; Parsons, JB; Fowler, VG; Rowe, SE; Conlon, BP
Published in: iScience
October 20, 2023

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, α-toxin, interacts with macrophages to alter the microenvironment of the pathogen, thereby influencing its susceptibility to antibiotics. We find α-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.

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Published In

iScience

DOI

EISSN

2589-0042

Publication Date

October 20, 2023

Volume

26

Issue

10

Start / End Page

107942

Location

United States
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Beam, J. E., Wagner, N. J., Lu, K.-Y., Parsons, J. B., Fowler, V. G., Rowe, S. E., & Conlon, B. P. (2023). Inflammasome-mediated glucose limitation induces antibiotic tolerance in Staphylococcus aureus. IScience, 26(10), 107942. https://doi.org/10.1016/j.isci.2023.107942
Beam, Jenna E., Nikki J. Wagner, Kuan-Yi Lu, Joshua B. Parsons, Vance G. Fowler, Sarah E. Rowe, and Brian P. Conlon. “Inflammasome-mediated glucose limitation induces antibiotic tolerance in Staphylococcus aureus.IScience 26, no. 10 (October 20, 2023): 107942. https://doi.org/10.1016/j.isci.2023.107942.
Beam JE, Wagner NJ, Lu K-Y, Parsons JB, Fowler VG, Rowe SE, et al. Inflammasome-mediated glucose limitation induces antibiotic tolerance in Staphylococcus aureus. iScience. 2023 Oct 20;26(10):107942.
Beam, Jenna E., et al. “Inflammasome-mediated glucose limitation induces antibiotic tolerance in Staphylococcus aureus.IScience, vol. 26, no. 10, Oct. 2023, p. 107942. Pubmed, doi:10.1016/j.isci.2023.107942.
Beam JE, Wagner NJ, Lu K-Y, Parsons JB, Fowler VG, Rowe SE, Conlon BP. Inflammasome-mediated glucose limitation induces antibiotic tolerance in Staphylococcus aureus. iScience. 2023 Oct 20;26(10):107942.
Journal cover image

Published In

iScience

DOI

EISSN

2589-0042

Publication Date

October 20, 2023

Volume

26

Issue

10

Start / End Page

107942

Location

United States