Synergistic breakthrough of Melissa officinalis L. Essential oil-loaded nanostructured lipid carrier for combating colistin resistance of MCR-1 positive Escherichia coli.

The global spread of multidrug-resistance (MDR) bacteria is devastating health systems and economies worldwide, and this critical trend has revitalized antibiotic adjuvant research. The extensive dissemination of plasmid- or chromosome-mediated resistance genes emphasize the importance of reshaping colistin sensitivity. Here, we report the discovery that Melissa officinalis essential oil isolated from Traditional Chinese medicine, effectively potentiates bactericidal activities of colistin against mobile colistin resistance (MCR-1) positive Escherichia coli (E. coli). Mechanistic analysis demonstrated that Melissa officinalis essential oil interacts with the MCR-1 protein to disrupt LPS modification, while concurrently inducing microbial iron homeostasis disruption and oxidative damage. To enhance its essential oil-mediated therapeutic potential in clinical management, Melissa officinalis essential oil-loaded nanostructured lipid carrier (MOEO-NLC) was designed with improved biocompatibility and solubility. Encouragingly, the combination of MOEO-NLC and colistin achieves bacterial burden reduction and inflammatory response suppression in a peritonitis-sepsis model. Collectively, this study advances antibacterial tactics and underscores the transformative potential of MOEO-NLC in paving the way for enduring countermeasures against antibiotic-resistant threats.