Abstract:[Background] Lexapeptide is the first member of the class V lanthipeptide family. In vitro bioassay indicated that lexapeptide has remarkable antibacterial activity against various G+ bacteria, and shows stronger activity against methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-resistant Staphylococcus epidermidis (MRSE) than nisin. Lexapeptide also exhibits better thermo-stability and pH-stability than nisin. The mode of actions of lexapeptide remains uncovered, hindering its potential application. [Objective] Through investigation into the antibacterial mode of action of lexapeptide to lay the foundation for its further application. [Methods] The antibacterial kinetics of lexapeptide was characterized by colony-forming unit (CFU) counting and magnesium ion assay. The pore forming ability of lexapeptide was assessed by flow cytometry (FCM) and transmission electron microscopy (TEM). High performance liquid chromatography (HPLC) and matrix assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) were used to analyze lexapeptide's effect on the accumulation of peptidoglycan biosynthetic precursor in G+ bacteria. [Results] Compared to nisin, the antibacterial activity of lexapeptide was less sensitive to the inhibition by magnesium ion. Bacterial cells treated with lexapeptide gained permealiability to fluorescent dye. Damaged morphology of those cells was observed with TEM. A peptidoglycan biosynthetic precursor, UDP-NAcMur-pentapeptide, was determined in the lexapeptide-treated cells.[Conclusion] Lexapeptide inhibits the growth of G+ bacteria by inhibiting the biosynthesis of peptidoglycan in cell wall as well as permeabilizing the cell membrane.
