Expanding the Spectrum: Modified Bacteriocin Nisin as a Trojan Horse Against Gram-Negative Salmonella Typhimurium and Escherichia coli

Abstract

Nisin is an antimicrobial peptide widely used as a biopreservative to extend shelf life and control foodborne pathogens, particularly Gram-positive bacteria such as Listeria monocytogenes. However, its efficacy against Gram-negative bacteria is limited due to its inability to penetrate their outer membrane and reach its target, lipid II, in the inner membrane. Agents that alter the outer membrane's permeability can overcome this limitation, enabling nisin to access the periplasm and expand its antimicrobial spectrum. In this study, we aimed to extend nisin's spectrum of action towards Gram-negative bacteria by fusing it with salmochelin, a siderophore produced by Salmonella. Siderophores capture extracellular iron and enter cells through specific receptors. The nisin-salmochelin conjugate was synthesized through an external chemical reaction, yielding a compound with activity against Gram-positive and Gram-negative bacteria. Among the Gram-negative bacteria, notable strains include Salmonella enterica Newport, S. enterica Typhimurium, Escherichia coli O157, E. coli EC3 (uropathogenic isolate), and Providencia rettgeri. This novel conjugate exhibits broad-spectrum activity against foodborne pathogens, significantly enhancing nisin's potential as a food biopreservative and expanding its clinical applications.