Enhanced antibacterial activity of organic acids via gallium chelation: a promising antibiotic alternative

As an alternative to antibiotics, acidifiers have gained widespread application in the feed industry. However, current acidifier products often suffer from limited antibacterial efficacy. To tackle this issue, we synthesized a series of organic acid - gallium complexes (Ga-OA) using organic acids (OA) and Ga ³⁺ as precursors, via a liquid-phase synthesis method. The antimicrobial activity of Ga-OA against Escherichia coli , Staphylococcus aureus , and Salmonella spp. was assessed using the Oxford cup and agar dilution methods to determine the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC), respectively. It was found that the Ga-OA complexes showed markedly higher antibacterial activity than each individually, and the antibacterial activity of Ga-OA complexes followed the order: Ga-Lac (lactic acid) > Ga-Ac (acetic acid) > Ga-BA (butyric acid). Furthermore, The MIC values of Ga-Lac against Escherichia coli, Staphylococcus aureus, and Salmonella spp were 2.84, 0.18, and 2.84 mmol/L, respectively, meanwhile, the MBC values of Ga-Lac against these three bacteria were 5.68, 1.42, and 5.68 mmol/L, respectively. Transcriptome analysis revealed that the antibacterial mechanism of Ga-OA is initiated by organic acid (OA) binding to bacterial membranes, which promotes Ga ³⁺ entry into the cell. This intracellular Ga³⁺ then disrupts iron transport, ultimately resulting in bacterial death. These results suggest that Ga-OA complexes have the potential to be a promising, safe, and effective antibacterial agent in animal husbandry, providing a solution to antibiotic resistance concerns.