1. Nicotine promotes Staphylococcus aureus-induced osteomyelitis by activating the Nrf2/Slc7a11 signaling axis.
- Author
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Zhou X, Ma S, Xu Y, Sun C, Liao J, Song M, Li G, Yuchen L, Chen P, Hu Y, Wang Y, and Yu B
- Subjects
- Animals, Mice, Mice, Inbred C57BL, Humans, Male, Phagocytosis drug effects, Disease Models, Animal, NF-E2-Related Factor 2 metabolism, Staphylococcus aureus drug effects, Nicotine pharmacology, Signal Transduction drug effects, Staphylococcal Infections drug therapy, Osteomyelitis microbiology, Osteomyelitis drug therapy, Osteomyelitis metabolism, Amino Acid Transport System y+ metabolism
- Abstract
Although smoking is a significant risk factor for osteomyelitis, there is limited experimental evidence that nicotine, a key tobacco constituent, is associated with this condition, leaving its mechanistic implications uncharacterized. This study revealed that nicotine promotes Staphylococcus aureus-induced osteomyelitis by increasing Nrf2 and Slc7a11 expression in vivo and in vitro. Inhibition of Slc7a11 using Erastin augmented bacterial phagocytosis/killing capabilities and fortified antimicrobial responses in an osteomyelitis model. Moreover, untargeted metabolomic analysis demonstrated that Erastin mitigated the effects of nicotine on S. aureus-induced osteomyelitis by altering glutamate/glutathione metabolism. These findings suggest that nicotine aggravates S. aureus-induced osteomyelitis by activating the Nrf2/Slc7a11 signaling pathway and that Slc7a11 inhibition can counteract the detrimental health effects of nicotine., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)
- Published
- 2024
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