Multiple Mechanisms of the Synthesized Antimicrobial Peptide TS against Gram-Negative Bacteria for High Efficacy Antibacterial Action In Vivo.

Rui Zhang,Xinglu Jiang,Mingyuan Zou,Han Xiao,Xiaobo Fan,Guoqiu Wu

doi:10.3390/molecules26010060

Rui Zhang, Xinglu Jiang + Show 4 more

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https://doi.org/10.3390/molecules26010060

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Abstract

The emergence of drug-resistant bacteria emphasizes the urgent need for novel antibiotics. The antimicrobial peptide TS shows extensive antibacterial activity in vitro and in vivo, especially in gram-negative bacteria; however, its antibacterial mechanism is unclear. Here, we find that TS without hemolytic activity disrupts the integrity of the outer bacterial cell membrane by displacing divalent cations and competitively binding lipopolysaccharides. In addition, the antimicrobial peptide TS can inhibit and kill E. coli by disintegrating the bacteria from within by interacting with bacterial DNA. Thus, antimicrobial peptide TS’s multiple antibacterial mechanisms may not easily induce bacterial resistance, suggesting use as an antibacterial drug to be for combating bacterial infections in the future.

Highlights

Most antimicrobial drugs inhibit and kill bacteria by mainly interfering with specific intracellular substances in important biochemical cell processes [1]
We find that antimicrobial peptide TS has stable physicochemical properties and plays an efficient bactericidal role through multiple mechanisms of action, which is important for facilitating the exploitation and use of new peptides for the treatment of clinical microbial infections and supporting the development of new antibiotics
Antimicrobial peptide TS exhibits significant antimicrobial activity against gram-negative bacteria, including the E. coli ATCC 25922 and K. pneumoniae ATCC 700603 strains at 1.6 μM for both for the minimum inhibitory concentration (MIC)

Summary

Introduction

Most antimicrobial drugs inhibit and kill bacteria by mainly interfering with specific intracellular substances in important biochemical cell processes [1]. Bacteria can develop resistance by reducing or modifying antibiotic targets. Beta-lactam antibiotics can bind to penicillin-binding proteins (PBPs), blocking the synthesis of cell wall mucin and resulting in the loss of the cell wall, expansion, and lysis of the bacteria, while gram-negative bacteria via porin mutations to resist antimicrobial drugs. Using antibiotics widely in humans and the use of antibiotics without an appropriate treatment causes resistances to develop quickly [2,3]. Pathogenic micro-organisms have exhibited dramatically increased resistances to most known antimicrobial drugs. In the era of drug resistance, the ability to control bacterial infections through antibiotics is weakened due to multidrug-resistant bacteria and the emergence of superbugs which could cause serious public health crises [4]. Due to the relatively slow development of new antibiotics, developing new, natural, and effective antibiotics with novel mechanisms is needed extremely urgently [5]

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