Cinnamaldehyde attenuates intergeneric horizontal transfer of antibiotic resistance genes by disrupting quorum sensing

Abstract

The rapid spread of antibiotic resistance genes (ARGs) via plasmid-driven conjugation in pathogenic microbes poses a pressing challenge to global health. Quorum sensing (QS) is pivotal in modulating processes such as biofilm development and the release of virulence determinants, which in turn affect ARG transmission. In this research, an interspecies conjugation model was constructed using Escherichia coli DH5α and Pseudomonas aeruginosa PAO1 as model strains to explore the impact of cinnamaldehyde, a naturally occurring quorum sensing inhibitor (QSI), on the conjugative transfer of antibiotic resistance genes (ARGs) under sub-inhibitory concentrations (sub-MICs). The results revealed that cinnamaldehyde at sub-MICs markedly suppressed transfer frequency without hindering bacterial proliferation. This inhibition of conjugation was largely linked to the suppression of biofilm formation and extracellular polymeric substance (EPS) production, downregulation of QS-related genes rhlI and rhlR, and reduced secretion of virulence factor rhamnolipid, thereby further restricting biofilm-associated ARG dissemination. These mechanisms are all under the governance of the QS system. These findings suggest that cinnamaldehyde, as a QSI, holds promising potential for controlling the spread of bacterial resistance and provides a novel strategy for regulating horizontal gene transfer of ARGs.

Graphical abstract

Keywords

Antibiotic resistance genes / Intergeneric conjugation / Cinnamaldehyde / Quorum sensing / Biofilm / Virulence factor

Highlight

	● The quorum sensing inhibitor cinnamaldehyde inhibited HGT of ARGs through conjugation.
	● Cinnamaldehyde inhibited conjugation of ARGs through regulating quorum sensing.
	● Quorum quenching suppressed biofilm formation, EPS secretion, and rhamnolipid release.
	● Downregulation of QS-related genes restricted biofilm-associated ARG transfer.
	● Cinnamaldehyde offers a sustainable strategy to mitigate the dissemination of ARGs.

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