Transition Metal-Weak Organic Acid Synergy Enables Rapid Bactericidal and sporicidal Activity

Abstract

The global rise in antibiotic-resistant bacteria underscores the urgent need for alternative antimicrobial strategies capable of limiting bacterial growth and viability. We previously demonstrated that weak organic acids and transition metals combine synergistically to strongly inhibit bacterial growth. Here, we extend these findings to determine whether this interaction results only in bacteriostatic suppression or can induce irreversible killing. Using standardized quantitative assays, selected acid-metal combinations achieved rapid bactericidal activity, producing >5-log reductions in Gram-negative and Gram-positive bacterial load after brief exposure at concentrations substantially lower than those required for many conventional disinfectants. This activity extended beyond vegetative cells. Bacillus cereus spores, used as a surrogate for spores of Bacillus anthracis, exhibited significant loss of viability under defined conditions. Given the environmental persistence of anthrax spores and their relevance in biological threat scenarios, these findings have implications not only for antimicrobial resistance mitigation but also for biodefense and environmental decontamination. Sporicidal efficacy was exposure dependent, with prolonged contact enabling effective killing at reduced concentrations. Together, these results establish acid-metal systems as scalable antimicrobial agents with bactericidal and sporicidal activity relevant to public health and global security. Importance statementAntibiotic resistance and the persistence of bacterial spores demand new antimicrobial strategies that are both effective and practical. This study shows that combining weak organic acids with transition metals transforms two modest antimicrobial agents into a powerful broad-spectrum killing system. These synergistic formulations rapidly eradicate Gram-negative and Gram-positive bacteria, achieving bactericidal activity at concentrations substantially lower than those used in many conventional disinfectants. Importantly, their activity extends to bacterial spores, among the most resilient biological structures known and a major challenge in environmental decontamination and biodefense. Using Bacillus cereus as a surrogate for Bacillus anthracis, we demonstrate dramatic sporicidal activity, reducing spore viability by up to six orders of magnitude. By coupling strong efficacy with a simple, scalable, and potentially environmentally compatible formulation, this work establishes transition metal-organic acid combinations as a promising new platform for infection control, environmental decontamination, and biodefense preparedness.