Microbial interactions of EDTA: recent advances and biological applications in the context of natural product modulation

Background and objectives: Ethylenediaminetetraacetic acid (EDTA) and its salts have been the choice of chelating agents since the 1940s. This review presents an updated details of their synthesis, general biology, ecotoxicological aspects, and applications as antimicrobial and antibacterial agents in combination with natural products. Methods: Relevant research papers were retrieved from PubMed, Web of Science, and Google Scholar through November 2025. Experimental uses of EDTA were excluded. The search terms used were "EDTA" AND "ECOTOXICOLOGY"; "EDTA" AND "GENOTOXICITY"; "EDTA" AND "ANTIMICROBIAL ACTIVITY"; "EDTA" AND "ANTIBACTERIAL ACTIVITY" AND "DENTAL" and "EDTA" AND "ANTICANCER ACTIVITY", "EDTA IN COMBINATION WITH NATURAL PRODUCTS". Results: Sodium/calcium salts of EDTA are water soluble, and their antiseptic efficacy is pH-dependent. They are effective against both Gram-positive and Gram-negative bacteria, as well as pathogenic yeasts, and adversely affect bacterial cell walls, thereby destabilizing biofilms. Multiple nature-derived compounds and standard antibiotics, in combination with EDTA and other therapeutic agents, minimize biofilms in intravascular and urinary catheters. It chelates various metal ions (including heavy metals) into a redox-inactive state, and thereby reduce their toxicity. Furthermore, it was shown to enhance the antimicrobial and antibacterial efficacy of various natural therapeutics when used together. Interpretation and conclusions: EDTA is a stable, readily available, affordable and comparatively safer chelating agent with antibacterial, antifungal, and antibiofilm properties. EDTA is now found to produce a synergistic effect when combined with natural therapeutics on their antimicrobial/antibiofilm activities. This approach proved fruitful in enhancing the capabilities of natural antibiotics against multidrug-resistant bacteria and in reducing the toxic effects of EDTA.