The antibacterial mode of action of lexapeptide

doi:10.13344/j.microbiol.china.210113

Home > Archive>Volume 48, Issue 7, 2021 >2355-2364. DOI:10.13344/j.microbiol.china.210113

The antibacterial mode of action of lexapeptide
DOI:
                        10.13344/j.microbiol.china.210113
                    
CSTR:
                        32113.14.j.MC.210113
                    
Author:
                        HONG JialiHONG Jiali
State Key Laboratory of Microbial Metabolism, Shanghai-Islamabad-Belgrade Joint Innovation Center on Antibacterial Resistances, Joint International Research Laboratory of Metabolic and Development Sciences, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200030, China
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WANG YeminWANG Yemin
State Key Laboratory of Microbial Metabolism, Shanghai-Islamabad-Belgrade Joint Innovation Center on Antibacterial Resistances, Joint International Research Laboratory of Metabolic and Development Sciences, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200030, China
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DENG ZixinDENG Zixin
State Key Laboratory of Microbial Metabolism, Shanghai-Islamabad-Belgrade Joint Innovation Center on Antibacterial Resistances, Joint International Research Laboratory of Metabolic and Development Sciences, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200030, China
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TAO MeifengTAO Meifeng
State Key Laboratory of Microbial Metabolism, Shanghai-Islamabad-Belgrade Joint Innovation Center on Antibacterial Resistances, Joint International Research Laboratory of Metabolic and Development Sciences, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200030, China
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[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.

Key words:lexapeptide;mode of action;lanthipeptide;nisin;peptidoglycan precursor;pore formation in cell membrane

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HONG Jiali, WANG Yemin, DENG Zixin, TAO Meifeng. The antibacterial mode of action of lexapeptide[J]. Microbiology China, 2021, 48(7): 2355-2364

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Received:January 28,2021
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Adopted:March 25,2021
Online: July 06,2021
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