A new study published in Engineering reveals that cinnamic acid, a widely used food additive found in cinnamon, can effectively inhibit plasmid‑mediated conjugation, a major route for the global spread of antibiotic resistance genes (ARGs). The research provides mechanistic insights into how this natural compound curtails horizontal gene transfer while maintaining high biosafety in living organisms.

Antimicrobial resistance remains a persistent global health challenge, with plasmid conjugation serving as a key driver for the dissemination of resistance determinants such as mcr‑1, bla_NDM‑1, and tet(X4) across bacterial populations. Current conjugation inhibitors often suffer from toxicity and limited in vivo performance, creating a demand for safer and more effective alternatives. In this work, researchers tested cinnamic acid (CA), a naturally occurring organic compound present in many plants and daily foods, across in vitro, ex vivo, and in vivo systems to evaluate its activity against clinically relevant plasmids including IncP, IncI2, IncX4, IncHI2, and IncFII types.

The team found that CA treatment reduced the conjugation frequency of multiple resistance plasmids in a concentration‑dependent manner without significantly affecting bacterial growth within the tested ranges. Using a fluorescence‑labeled plasmid‑tracing system, the investigators further confirmed that CA suppresses plasmid transfer within intestinal microbial communities ex vivo. In mouse models, oral administration of CA lowered in vivo conjugation frequency in a dose‑dependent way, demonstrating its activity under physiological conditions.

Transcriptomic analysis indicated that CA disrupts the tricarboxylic acid cycle, which in turn impairs the electron transport chain and dissipates proton motive force. These metabolic disturbances lead to decreased intracellular ATP levels, a critical energy source for the conjugation process. CA also downregulates the expression of key genes involved in mating pair formation and DNA transfer and replication systems, while slightly increasing outer membrane permeability in donor cells.

Biocompatibility assessments showed no obvious adverse effects in mice following CA administration, with no significant changes in body weight or histopathological features of major organs. Gut microbiota diversity and composition remained stable, supporting CA’s favorable safety profile for potential in vivo applications.

These findings suggest cinnamic acid acts as a broad‑spectrum conjugation inhibitor that targets bacterial energy metabolism to limit ARG spread. As a widely consumed food component with established safety, CA offers a feasible strategy to complement existing efforts against the rise of antibiotic‑resistant infections. The study supports further development of natural, metabolism‑targeted compounds to control horizontal gene transfer in clinical, agricultural, and environmental settings.

The paper “Targeting Plasmid Conjugation with Cinnamic Acid: A Novel Approach to Combat Antibiotic Resistance,” is authored by Gong Li, Ang Gao, Xin-Yi Lu, Tian-Hong Zhou, Shi-Ying Zhou, Li-Juan Xia, Lei Wan, Yu-Zhang He, Xin-Yi Chen, Wen-Ying Guo, Jia-Min Zheng, Hao Ren, Sheng-Qiu Tang, Xiao-Ping Liao, Liang Chen, Jian Sun. Full text of the open access paper: https://doi.org/10.1016/j.eng.2025.06.040. For more information about Engineering, visit the website at https://www.sciencedirect.com/journal/engineering.