Assoc. Prof.Dr.
Tran Quang Huy

Title: Inhibitory activity and action mechanism of Berberine against Gram-positive and -negative bacterial pathogens

Tran Quang Huy¹, Nguyen Thi Hue¹, Nguyen Thi Thu Thuy¹, Tran Khanh Hoan¹, Pham Thanh Tri²

¹Phenikaa University, Hanoi, Vietnam

²Nazarbayev University, Kazakhstan

Abstract

The emergence of antimicrobial resistance has stimulated interest in alternative antibacterial agents derived from natural products. Berberine (BBR), a bioactive isoquinoline alkaloid, possesses broad-spectrum antimicrobial properties; however, its antibacterial spectrum and cellular targets remain incompletely understood. This study evaluated the antimicrobial efficacy of berberine against clinically relevant Gram-positive and Gram-negative bacterial species and investigated their mechanism of action using ultrastructural analysis. Antibacterial susceptibility testing revealed marked differences in BBR sensitivity among bacterial taxa. Rod-shaped Gram-negative bacteria, including Escherichia coli and Pseudomonas aeruginosa, as well as the rod-shaped bacteria Bacillus subtilis and Lactobacillus plantarum, exhibited only partial growth inhibition following BBR exposure. In contrast, the Gram-positive bacteria including Staphylococcus aureus and Staphylococcus epidermidis demonstrated high susceptibility with significant growth and complete bactericidal activity less than 0.2 mg/mL. Notably, the Gram-negative strain of Moraxella catarrhalis revealed exceptional sensitivity to BBR, with complete bacterial activity observed at a concentration as low as 0.016 mg/mL. These findings suggest that bacterial susceptibility to BBR may be influenced not only by Gram-staining characteristics but also by cellular morphology and envelope architecture. To study the antibacterial mechanism, transmission electron microscopy (TEM) combined with ultrathin-section analysis was performed. Ultrastructural examination revealed extensive membrane damage in BBR-treated cells, characterized by disruption of cell envelope integrity, cytoplasmic disorganization, and leakage of intracellular contents. These morphological alterations indicate that the bacterial cell membrane represents a primary target of BBR-mediated antibacterial activity. In summary, the results demonstrate potent bactericidal effects of BBR against selected bacterial pathogens, particularly spherical-shaped species, and provide direct ultrastructural evidence supporting membrane-targeted antibacterial mechanisms. These findings highlight the therapeutic potential of BBR-based drugs as alternative antimicrobial agents for the management of bacterial infections.

Keywords: Berberine; BBR; antibacterial activity rod-shaped Gram-negative bacteria; spherical-shaped Gram-positive bacteria; antibacterial mechanism

Biography of the presenting author:

Associate Professor Tran Quang Huy is a researcher and faculty member at Phenikaa University, Vietnam. Currently, he is a vice director of Phenikaa University Nano Institute and also Head of the Department of Physiology and Functional Investigation, Faculty of Biomedical Sciences, Phenikaa School of Medicine and Pharmacy. His research interests include medical microbiology, biophysics, nanomedicine, antimicrobial nanomaterials, biosensors, drug delivery systems, and advanced imaging technologies. With more than 20 years of research experience, he has published more than 100 papers in peer-reviewed international journals and actively promotes scientific collaboration in medical microbiology, microscopy, biophysics, and biomedical sciences throughout Vietnam and Southeast Asia.

Presenting author details:

Full name: Assoc. Prof.Dr. Tran Quang Huy

Email: huy.tranquang@phenikaa-uni.edu.vn

Google Scholar: https://scholar.google.com.vn/citations?user=hshDeNEAAAAJ&hl=en