Linalool Disrupts Escherichia coli Biofilms via Dual Suppression of Motility and Adhesion

Lei Wang^1*Jingyan Zhang¹Guowei Xu¹Zhiting Guo¹Jiamian Wang¹Liping Huang¹Lei Wei¹Long Wang²Kang Zhang¹Jianxi Li^1*

• ¹Chinese Academy of Agricultural Sciences Lanzhou Institute of Husbandry and Pharmaceutical Sciences, Lanzhou, China
• ²Zhengzhou Products Quality Inspection and Testing Center, Zhengzhou, China

Bacterial biofilms, characterized by robust antibiotic resistance and involvement in chronic infections, present significant clinical challenges such as endometritis. While linalool as a natural compound exhibits potent antibiofilm properties, its precise mechanisms of action against Escherichia coli (E. coli) remain unclear. This study revealed linalool's dual-action mechanism in inhibiting E. coli D5 biofilm formation by suppressing motility and blocking adhesion. In vitro assays demonstrated concentration-dependent biofilm inhibition by linalool, achieving 99% inhibition at 4 µL/mL, with structural disintegration confirmed through scanning electron microscopy. Mechanistically, linalool disrupted flagellar gene regulation, downregulating fliA and motA while upregulating fliG and fliM, and impaired both swarming and swimming motility. Simultaneously, it suppressed fimbriae-associated genes (csgA, csgD, and fimH), leading to 99% reduction in bacterial adhesion to bovine endometrial epithelial cells and the eradication of 95% of intrauterine biofilms in vivo. As a low-toxicity phytochemical, linalool represents a potent multitarget agent against biofilm-associated infections. Future studies should validate its pharmacodynamics and potential synergies with conventional antibiotics to facilitate clinical application.