1. Academic Validation
  2. Combining Colistin with Furanone C-30 Rescues Colistin Resistance of Gram-Negative Bacteria in Vitro and in Vivo

Combining Colistin with Furanone C-30 Rescues Colistin Resistance of Gram-Negative Bacteria in Vitro and in Vivo

  • Microbiol Spectr. 2021 Dec 22;9(3):e0123121. doi: 10.1128/Spectrum.01231-21.
Ying Zhang 1 Yishuai Lin 2 Xiaodong Zhang 1 Liqiong Chen 2 Chunyan Xu 1 Shixing Liu 1 Jianming Cao 2 Xiangkuo Zheng 1 Huaiyu Jia 2 Lijiang Chen 1 Tieli Zhou 1
Affiliations

Affiliations

  • 1 Department of Clinical Laboratory, The First Affiliated Hospital of Wenzhou Medical Universitygrid.414906.e, Wenzhou, China.
  • 2 Department of Medical Lab Science, School of Laboratory Medicine and Life Science, Wenzhou Medical University, Wenzhou, China.
Abstract

The spread of multidrug-resistant (MDR) Gram-negative bacteria (GNB) has led to serious public health problems worldwide. Colistin, as a "last resort" for the treatment of MDR Bacterial infections, has been used significantly in recent years and has led to the continuous emergence of colistin-resistant strains. In this study, we aimed to investigate the synergistic effect on the antimicrobial and antibiofilm activities of a colistin/furanone C-30 combination against colistin-resistant GNB in vitro and in vivo. According to antimicrobial resistance profiles, most of the colistin-resistant strains we collected showed MDR phenotypes. The checkerboard method and time-kill curve showed that the combination with furanone C-30 increases the Antibacterial activity of colistin significantly. In addition, the furanone C-30/colistin combination can not only inhibit the formation of Bacterial biofilm but also has a better eradication effect on preformed mature biofilms. The result of scanning electron microscopy (SEM) demonstrated that the furanone C-30/colistin combination led to a significant reduction in the number of cells in biofilms. Furthermore, furanone C-30 at 50 μg/ml did not cause any additional toxicity to RAW264.7 cells according to a cytotoxicity assay. In in vivo Infection experiments, the furanone C-30/colistin combination increased the survival rate of infected Galleria mellonella larvae as well as decreased the microbial load in a mouse thigh Infection model. The synergistic effect of the furanone C-30/colistin combination against colistin-resistant GNB is encouraging, and this work may shed LIGHT on a new therapeutic approach to combat colistin-resistant pathogens. IMPORTANCE Colistin is among the few Antibiotics effective against multidrug-resistant Gram-negative bacteria (GNB) clinical isolates. However, colistin-resistant GNB strains have emerged in recent years. Therefore, the combination of colistin and nonantibacterial drugs has attracted much attention. In this study, the furanone C-30/colistin combination showed good Antibacterial and antibiofilm activity in vitro and in vivo. In addition, increased membrane permeability leads to the synergistic effect of the furanone C-30/colistin combination. Because of the low cytotoxicity of furanone C-30, this combination has good application prospects in clinical anti-infective therapy. This finding might shed LIGHT on the discovery of combination therapy for infections caused by colistin-resistant GNB pathogens.

Keywords

Gram-negative bacteria; biofilm; colistin-resistant; furanone C-30; multidrug resistance; synergy effect.

Figures
Products