Combining Bile Salt with Gentamicin: A Promising Strategy Against Vibrio Parahaemolyticus and Escherichia Coli

Vibrio parahaemolyticus and Escherichia coli have expanded their pathogenicity and transmission range, developed resistance to various antibiotics and have the ability to form biofilms, posing a serious challenge to the clinical application of traditional antibiotics. To address this crisis of antibiotic resistance, the urgent need for natural, alternative or adjunctive strategies has become paramount. Bile salts exhibit potential value as a natural antimicrobial agent. The aim of this study was to explore the potential of bile salts as an antibiotic adjuvant to reduce the amount of antibiotics used and thus antibiotic resistance, and to provide new strategies for the treatment of infections. The fractional inhibitory concentration index (FICI) of bile salts with antibiotics was determined, with the combination with gentamicin (GEN) exhibited the most efficient synergistic antibacterial effects. Additionally, this combination significantly inhibited biofilm formation (83.76% and 60.98%) and reduced the production of extracellular polysaccharides and proteins. Further investigation demonstrated that this combination notably induced leakage of intracellular enzymes (e.g. alkaline phosphatase and β-galactosidase), and resulted in an elevation of the intracellular reactive oxygen species (ROS) levels. This phenomenon could be ascribed to the fact that bile salts significantly increased the membrane permeability, thus facilitating the penetration of GEN into bacterial cells. Therefore, the combination of bile salts and GEN triggered severe intracellular oxidative damage and irreversible cell membrane disruption, ultimately leading to bacterial death. The synergistic effect between bile salts and GEN offers a promising strategy for the treatment of foodborne pathogens.