Cell Membrane-Targeted Antibacterial Synergy of Citric Acid–Sodium Hypochlorite Against Salmonella Typhimurium on Cherry Tomatoes

Foodborne illness outbreaks from fresh produce underscore the urgent demand for sanitizing strategies that ensure safety while minimizing harmful by-products from high-dose chemical disinfectants such as sodium hypochlorite (NaOCl). Low-concentration combinations of organic acids and washing sanitizers were systematically evaluated to identify synergistic antibacterial effects, and citric acid (CA) was found to markedly potentiate the activity of NaOCl against Salmonella Typhimurium through a sequential assault on the cell envelope. A low-dose combination of sub-inhibitory concentrations (1/2 MIC of CA and 1/4 MIC of NaOCl) exhibited robust synergy, achieving a >6 log CFU/cm2 reduction in the pathogen on a cherry tomato model within 3 min. Moreover, this synergistic entry leads to profound disruption of membrane integrity, resulting in leakage of nucleic acids and proteins, extensive oxidative damage, hyperpolarization, and cell lysis, as confirmed by electron and confocal microscopy together with physicochemical assays. Mechanistic investigation revealed that oxidative damage from NaOCl amplified CA-induced membrane acidification and permeability, facilitating deeper sanitizer penetration and accelerating envelope destruction. Collectively, these findings uncover a membrane-targeted synergistic mechanism, providing a solid scientific basis for the development of novel, low-residue, and high-efficacy food safety interventions.