Mechanisms of action of berberine hydrochloride in planktonic cells and biofilms of Pseudomonas aeruginosa

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Abstract
The growing prevalence of extensive drug-resistant and pan-drug resistant Pseudomonas aeruginosa (P. aeruginosa) has become a significant concern for global public health, particularly due to the formation of biofilms. Consequently, it is crucial to explore the development of novel antimicrobials that specifically target P. aeruginosa and its biofilms. Here we found a natural compound named berberine hydrochloride, subsequently, Crystalline violet staining and Confocal laser scanning microscope further demostrated that berberine hydrochloride suppress biofilm. Additionally, it was found that the expression of pslA and other biofilm-related genes were downregulated. Compared with available antibiotics, berberine hydrochloride has multiple modes of action in P. aeruginosa. The antimicrobial mechanism showed that berberine hydrochloride might have antimicrobial effects by damaging bacterial cell membranes, generating reactive oxygen species (ROS) and lowering intracellular adenosine triphosphate (ATP). Futhermore, berberine hydrochloride possesses various attributes, including minimal cytotoxicity and reduced susceptibility to drug resistance. In a mice peritonitis model, it was reported to inhibit the growth of P. aeruginosa significantly and displayed high bacteriostatic action. Collectively, the berberine hydrochloride is a safe and effective antibacterial agent for inhibiting P. aeruginosa.

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