α-Pinene: Inhibitor of Acinetobacter baumannii biofilms and potential therapeutic agent for pneumonia

Abstract

Acinetobacter baumannii is a Gram-negative bacterium whose biofilm formation and mechanisms contribute to its persistent infectivity and drug resistance in clinical settings. Inhibition or disruption of biofilms might hold the key to resolving the issue of drug resistance in A. baumannii. α-Pinene, a bicyclic terpene olefin derived from the essential oils of plants, exhibits multiple biological activities, including antimicrobial, antioxidant, and anti-inflammatory effects. In this investigation, we discovered that α-Pinene had powerful antimicrobial activity against A. baumannii 390015, and its minimum inhibitory concentration was 0.625 μL/mL. In vitro experiments demonstrated that α-Pinene exerted an inhibitory effect on biofilm formation and impacted the production of extracellular polymers and the twitching motility of A. baumannii. Moreover, qRT-PCR experiments in combination with proteomic validation revealed that bmfR, csuAB, ompA, and bap were down-regulated in A. baumannii after the action of α-Pinene. In vivo experiments indicated that α-Pinene decreased the expression of inflammatory factors, including interleukin 6 (IL-6) and tumor necrosis factor-α (TNF-α) in tissues. Additionally, the expression levels of JNK, P38, and ERK in the downstream pathways of TRAF6 were evaluated, and it was found that α-Pinene decreased the expression levels of JNK, P38, and ERK. Notably, the expression levels of these markers increased as the concentration of α-Pinene decreased. These findings suggest that α-Pinene can inhibit biofilm formation in A. baumannii and mitigate inflammation, highlighting its therapeutic potential for A. baumannii infections.