Diverse Uses of Lantibiotics: Exploring New Approaches to Combat Antibiotic Resistance

ABSTRACT

Rising multidrug resistance demands novel antimicrobials. Lantibiotics are ribosomally synthesized peptides with unique post‐translational modifications (including lanthionine) that confer potent bactericidal activity against Gram‐positive species. Their membrane‐disruptive and cellular inhibitory mechanisms make them promising candidates for next‐generation antibiotics to combat escalating antibiotic resistance. Lantibiotics exhibit a synergistic dual mode of action through binding to lipid II, a conserved peptidoglycan precursor essential for bacterial cell wall synthesis. This interaction inhibits peptidoglycan assembly and compromises the integrity of the cell wall, causing the cytoplasmic membranes to develop lipid II‐mediated pores, which result in ion leakage, membrane depolarization, and rapid bacterial death. Compared with single‐target antimicrobial drugs, the interdependence of these processes in lantibiotics provides a significant advantage against drug‐resistant bacteria by lowering the likelihood of resistance development. Naturally occurring lantibiotics from bacteria such as Lactococcus and Streptomyces have gained attention for therapeutic and preservation uses. This review summarizes their types, sources, structures, functions, variants, and potential applications in combating antibiotic‐resistant bacteria. Although progress is limited by pharmacokinetic and spectrum challenges, modifying natural lantibiotic scaffolds offers validated mechanisms, established efficacy, and accessible bioengineering routes for antibacterial development. In contrast, de novo drug design involves higher translational risk and complexity but enables rational creation of agents with improved stability, resistance profiles, and potential activity against Gram‐negative bacteria. This review supports the identification of novel therapeutic agents for eliminating drug‐resistant microorganisms.