Colistin Enhances Antimicrobial Activity against colistin-resistant Klebsiella pneumoniae by combined with the Chinese herbal crocin-1

Abstract

Abstract Background Colistin (COL) is one of the last-line antibiotics of defense against multidrug-resistant (MDR) gram-negative bacteria However, colistin-resistant (Col-R) Klebsiella pneumoniae (K. pneumoniae) is increasing, which limits the clinical use of COL. Saffron is a traditional Chinese medicine with the effects of promoting blood circulation and removing blood stasis, relieving depression and calming the nerves, protecting the liver and promoting the gallbladder. Croin-1(CR) is an active ingredient extracted from saffron. In this study, we studied the antibacterial effects of CR and COL on Col-R K. pneumonia in vivo and in vitro. Methods The checkerboard method and time-killing curve confirmed the synergistic antibacterial effect of CR combined with COL on Col-R K. pneumonia. The synergistic anti-biofilm and antibacterial activity were detected by crystal violet staining, scanning electron microscopy (SEM), and living cell fluorescent staining. The safety was assessed by the red blood cells (RBCs) hemolysis test, larval survival rates, and cytotoxicity test. The mice thigh infection model was established for in vivoexperiment. We determined the outer membrane permeability by measuring the uptake of fluorescent dye N-phenyl-1-naphthylamine(NPN) and propidium iodide (PI) staining. We further detected bacterial reactive oxygen species (ROS) production. ResultsThe Results showed that compared with a single drug, the combination partially destroyed bacterial cells and inhibited the formation of bacterial biofilms. The CR/COL combination could decrease the number of bacteria after 24 h of therapy in the mouse thigh infection model. The CR/COL combination synergistically potentiated the antibacterial activity by accelerating the damage and permeability of the bacterial outer membrane. Erythrocytes hemolysis test showed that the hemolysis ability of CR was negligible. Therefore, CR has certain security. Conclusions According to our results, CR can enhance the antibacterial effect of colistin against Col-R K. pneumonia, which may provide a feasible strategy for the fight against Col-R K. pneumonia.