Modification of acidocin peptide with enhanced antimicrobial activity against foodborne pathogen, Salmonella enterica serovar Typhimurium

Among foodborne Salmonella causing salmonellosis, Salmonella enterica serovar Typhimurium (S. enterica serovar Typhimurium) is the most frequently found serovar globally. The main reason of human infections with S. enterica serovar Typhimurium is the consumption of contaminated foods, notably eggs, meat, and milk. This raises the awareness of consumers to have good hygiene practices and urging the development of new preservatives to ensure food safety, avoid any loss during food processing, transportation and prolong the shelf life. One of promising compounds is antimicrobial peptide (AMP) which showed a potential to be developed as a new class of food preservative agents besides nisin, the only approved antimicrobial peptide used currently. Among them, bacteriocins produced by lactic acid bacteria (LAB) have attracted increasing attention, since they are recognized as safe for human use with low or no toxicity. Acidocin J1132β a bacteriocin produced by probiotic Lactobacillus acidophilus, displayed no toxic activity to human, however it exhibited low and narrow-spectrum antimicrobial activity. To overcome this obstacle and further exploit it as food preservatives, modification of this peptide is challenging yet feasible. Based on key structural and physicochemical parameters, four peptide derivatives (A5, A6, A9, and A11) were modified from acidocin J1132β by truncation and amino acid substitution. Among them, A11 showed the highest antimicrobial activity especially against S. enterica serovar Typhimurium, with a favorable safety profile. It tended to form an α-helix structure upon encountering the negatively charged-mimicking environments. A11 caused transient membrane permeabilization and killed bacterial cells through membrane depolarization and/or intracellular mechanism as observed by its interaction with bacterial DNA. A11 mostly maintained its inhibitory effect even exposure to high temperature up to 100°C. Notably, it exhibited inhibitory effect toward drug-resistant foodborne S. enterica serovar Typhimurium and its monophasic variant strains. Furthermore, the combination of A11 with nisin showed synergistic effect against drug-resistant strains in vitro. In food preservation assay, the growth rate of S. enterica serovar Typhimurium in raw chicken meat was significantly reduced by the combined use of A11 with nisin treatment during 72 hours of refrigerated storage. Taken together, this study indicated that a novel antimicrobial peptide derivative modified from acidocin J1132β, A11, could be applied potentially in the food industry as a food bio-preservative to control the S. enterica serovar Typhimurium contamination in food processing.