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

• DOI: 10.1128/spectrum.01231-21
• Publication Date: 2021-11-03T14:30:45Z
• Authors: Ying Zhang; Yishuai Lin; Xiaodong Zhang; Liqiong Chen; Chunyan Xu; Shixing Liu; Jianming Cao; Xiangkuo Zheng; Huaiyu Jia; Lijiang Chen; Tieli Zhou
• Keywords: Colistin; Gram-Negative Bacteria; Gram; MCR-1; Gram-negative bacterial infections

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