Synergistic Inhibitory Effect of Honey and Lactobacillus plantarum on Pathogenic Bacteria and Their Promotion of Healing in Infected Wounds

Prevention and control of infections have become a formidable challenge due to the increasing resistance of pathogens to antibiotics. Probiotics have been discovered to have positive effects on the host, and it is well-known that some Lactobacilli are effective in treating and preventing inflammatory and infectious diseases. In this study, we developed an antibacterial formulation consisting of honey and Lactobacillus plantarum (honey-L. plantarum). The optimal formulation of honey (10%) and L. plantarum (1 × 10⁹ CFU/mL) was used to investigate its antimicrobial effect and mechanism in vitro, and its healing effect on wound healing of whole skin infections in rats. Biofilm crystalline violet staining and fluorescent staining results indicated that the honey-L. plantarum formulation prevented the biofilm formation in Staphylococcus aureus and Pseudomonas aeruginosa and increased the number of dead bacteria in the biofilms. Further mechanism studies revealed that the honey-L. plantarum formulation may inhibit biofilm formation by upregulating biofilm-related genes (icaA, icaR, sigB, sarA, and agrA) and downregulating quorum sensing (QS) associated genes (lasI, lasR, rhlI, rhlR, and pqsR). Furthermore, the honey-L. plantarum formulation decreased the number of bacteria in the infected wounds of rats and accelerated the formation of new connective tissue to promote wound healing. Our study suggests that the honey-L. plantarum formulation provides a promising option for the treatment of pathogenic infections and wound healing.