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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
Runping Zhao Runping Zhao 1Xu Lei Xu Lei 1Jieyun Chen Jieyun Chen 2Yanxian Yang Yanxian Yang 3Xilong Guo Xilong Guo 2Min Dai Min Dai 1Guo-bao Tian Guo-bao Tian 2*Lina Qin Lina Qin 4*
  • 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

The final, formatted version of the article will be published soon.

    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

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.