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ORIGINAL RESEARCH article
Front. Microbiol.
Sec. Antimicrobials, Resistance and Chemotherapy
Volume 15 - 2024 |
doi: 10.3389/fmicb.2024.1450085
Itaconate induces tolerance of Staphylococcus aureus to aminoglycoside antibiotics
Provisionally accepted- 1 School of Laboratory Medicine, Chengdu Medical College, Chengdu, China
- 2 Advanced Medical Technology Center, The First Affiliated Hospital, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China
- 3 Department of Pharmacy, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, Guangdong Province, China
- 4 Faculty of Forensic Medicine, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China
Staphylococcus aureus (S. aureus) is one of the main pathogens that cause chronic and recurrent infections. Failure of antibiotics to eradicate infections is an important reason for the high mortality rate and contributes to relapse. Treatment failure may be due to antibiotic tolerance. In this study, we found that the immune metabolite itaconate can induce tolerance in both methicillin-resistant and -susceptible S. aureus to aminoglycosides. When S. aureus was exposed to itaconate, its growth slowed down and displayed transcriptomic and metabolomic alterations associated with decreased energy metabolism, including the tricarboxylate cycle, glycolysis, pyruvate metabolism, and arginine biosynthesis. These changes are associated with aminoglycosides tolerance. This work highlighted the role of immune signaling metabolites in bacterial antibiotic tolerance and suggested new strategies to improve antibiotic treatment for by modulating the host immune response and stimulating the metabolism of bacteria.
Keywords: Staphylococcus aureus, Itaconate, antibiotic tolerance, Aminoglycosides, Immune metabolite
Received: 16 Jun 2024; Accepted: 09 Sep 2024.
Copyright: © 2024 Zhao, Lei, Chen, Yang, Guo, Dai, Tian and Qin. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Guo-bao Tian, Advanced Medical Technology Center, The First Affiliated Hospital, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China
Lina Qin, Faculty of Forensic Medicine, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China
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