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Exploiting the synergistic antibacterial activity of shikimic acid and ceftiofur against methicillin-resistant Staphylococcus aureus

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Abstract

Efforts to curtail the escalating health threat posed by methicillin-resistant Staphylococcus aureus (MRSA), a formidable superbug, necessitate the development of innovative treatment strategies. Leveraging potential compounds from natural sources in tandem with antibiotics has emerged as a promising approach against MRSA. These strategies should enhance the antibiotic efficacy, reduce dosage and toxicity, and bypass MRSA resistance. In this study, we used a checkerboard assay to illustrate the significant synergistic anti-MRSA effect of shikimic acid (SA), a naturally occurring compound, and ceftiofur (CF). Time-kill curves further revealed that a combination of 1/4 of the minimum inhibitory concentration (MIC) of SA and 1/8 MIC of the sodium CF eradicated MRSA within 2 h, with no noticeable toxicity observed with these concentrations. In vivo experiments confirmed that this combination therapy demonstrated robust antimicrobial activity against MRSA-induced bacteremia in mice, significantly reducing bacterial loads in the kidneys, liver, and spleen, attenuating inflammatory cell infiltration, and alleviating pathological damage. This study not only offers a compelling strategy, capitalizing on the synergistic potential of SA and CF, to rapidly address antibiotic resistance but also contributes significantly to the refinement of antimicrobial therapeutic strategies.

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Data availability

The datasets generated and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Funding

This work was supported by grants from the Department of Science and Technology of Hunan Province to Xiaofeng Zheng (2019RS1050 and 2021JJ30354) and a grant from the Department of Science and Technology of Hunan Province to Pishun Li (2023JJ30291).

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Author notes

  1. Zhuohui Zhang and Qianqian Xu have equally contributed to this work.

Authors and Affiliations

  1. College of Veterinary Medicine, Hunan Agricultural University, Changsha, 410128, China

    Zhuohui Zhang, Qianqian Xu, Yan Wang, Shiyin Qu, Junjie Tan, Pishun Li & Xiaofeng Zheng

  2. Hunan Engineering Technology Research Center of Veterinary Drugs, Hunan Agricultural University, Changsha, 410128, China

    Zhuohui Zhang, Qianqian Xu, Yan Wang, Shiyin Qu, Junjie Tan, Pishun Li & Xiaofeng Zheng

  3. Institute of Subtropical Agriculture, Chinese Academy of Sciences, Changsha, 410125, China

    Yulong Tang

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  1. Zhuohui Zhang
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  3. Yan Wang
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  4. Shiyin Qu
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Contributions

Material preparation, data collection and analysis were performed by ZZ, QX, SQ, JT and YT; The first draft of the manuscript was written by ZZ; YW and PL revised the manuscript; XZ and ZZ conceived and designed the experiments. All authors read and approved the final manuscript.

Corresponding authors

Correspondence to Pishun Li or Xiaofeng Zheng.

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The authors declare no competing interests.

Ethical approval

The animal work in this report was approved by the Experimental Animal Ethics Committee of the Institute of Subtropical Agriculture, Chinese Academy of Science (IACUC#201302), Date of approval: 21 April 2018, and it complied with the regulations on the use of experimental animals.

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Zhang, Z., Xu, Q., Wang, Y. et al. Exploiting the synergistic antibacterial activity of shikimic acid and ceftiofur against methicillin-resistant Staphylococcus aureus. World J Microbiol Biotechnol 40, 78 (2024). https://doi.org/10.1007/s11274-023-03876-x

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