2. Academic Validation
  3. Synergy with Farnesol Rejuvenates Colistin Active against Col-R Gram-Negative Bacteria in Vitro and in Vivo

Synergy with Farnesol Rejuvenates Colistin Active against Col-R Gram-Negative Bacteria in Vitro and in Vivo

  • Int J Antimicrob Agents. 2023 Jun 22;106899. doi: 10.1016/j.ijantimicag.2023.106899.
Yijia Han 1,  Yi Zhang 2,  Weiliang Zeng 3,  Zeyu Huang 3,  Haojun Cheng 2,  Jingchun Kong 2,  Chunquan Xu 3,  Mengxin Xu 3,  Tieli Zhou 4,  Jianming Cao 5
Affiliations

Affiliations

  • 1 School of Laboratory Medicine and Life Science, Wenzhou Medical University, Wenzhou, China; Department of Clinical Laboratory, The First Affiliated Hospital of Wenzhou Medical University; Key Laboratory of Clinical Laboratory Diagnosis and Translational Research of Zhejiang Province.
  • 2 School of Laboratory Medicine and Life Science, Wenzhou Medical University, Wenzhou, China.
  • 3 Department of Clinical Laboratory, The First Affiliated Hospital of Wenzhou Medical University; Key Laboratory of Clinical Laboratory Diagnosis and Translational Research of Zhejiang Province.
  • 4 Department of Clinical Laboratory, The First Affiliated Hospital of Wenzhou Medical University; Key Laboratory of Clinical Laboratory Diagnosis and Translational Research of Zhejiang Province. Electronic address: wyztli@163.com.
  • 5 School of Laboratory Medicine and Life Science, Wenzhou Medical University, Wenzhou, China. Electronic address: wzcjming@163.com.
PMID: 37354920 DOI: 10.1016/j.ijantimicag.2023.106899
Abstract

Colistin is considered the last line of treatment against infections due to multidrug-resistant (MDR) Gram-negative bacteria (GNB). However, the increasing number of colistin-resistant (Col-R) bacteria caused by the use of colistin is a great threat to public health. In this study, we proposed a strategy of combining farnesol (FAR), which has anti-inflammatory and antitumor properties, with colistin to restart colistin activity. We investigated the synergistic effect of FAR combined with colistin against Col-R GNB in vivo and in vitro. The excellent synergistic Antibacterial activity of the colistin-FAR combination was confirmed by performing the checkerboard assay, time-killing assay, and LIVE/DEAD Bacterial cell viability assay. Crystal violet staining and scanning electron microscopy results showed that colistin-FAR prevented biofilm formation and eradicated preexisting mature biofilm. Cytotoxicity assay showed that FAR at 64 μg/mL was not cytotoxic to RAW264.7 cells. In vivo Infection experiments showed that colistin-FAR increased the survival rate of infected Galleria mellonella and decreased the Bacterial load in the thigh of a mouse Infection model. Our results showed that the combination of colistin-FAR has a promising application prospect and can be an effective therapeutic option for combating Col-R GNB infections.

Keywords

Gram-negative bacteria; biofilm; colistin-resistant; farnesol; synergy mechanism.

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