Citronellol Potentiates Antibiotics Against Escherichia coli O157:H7 via Inhibition of Biofilm Formation

Abstract

The rise in antimicrobial resistance (AMR) demands new treatments, especially for biofilm-associated infections where bacteria tolerate antibiotics. Escherichia coli O157:H7 (E. coli O157) is a virulent foodborne pathogen that causes severe haemorrhagic colitis and haemolytic uraemic syndrome. The LuxS/AI-2 quorum sensing (QS) system regulates both biofilm formation and motility in this pathogen. Here, we used a luxS-eGFP reporter to screen for QS modulators and identified citronellol as a potent candidate. Citronellol disrupts biofilm formation and swimming motility. These effects were accompanied by reduced luxS expression and modulation of lsr operon genes, consistent with interference with LuxS/AI-2 signalling. As a result, citronellol enhanced the antibacterial activity of conventional antibiotics at sub-MIC doses. Importantly, the citronellol–fosfomycin combination improved survival and reduced hepatic bacterial burden in a murine systemic infection model. These benefits are correlated with restored intestinal barrier integrity, including upregulated tight junction proteins (ZO-1 and Occludin). Together, these results support the continued development of citronellol-based combinations as promising anti-biofilm strategies.