Abstract
In recent years, the overuse of antibiotics has become very serious. Many pathogenic bacteria have become resistant to them, with serious potential health consequences. Thus, it is urgent that we develop new antibiotic drugs. Antimicrobial peptides (AMPs) are important endogenous antibacterial molecules that contribute to immunity. Most have spectral antibacterial properties and do not confer drug resistance. In this paper, an 11-residue peptide (LFcinB18–28) with a sequence of KCRRWQWRMKK was modified by amino acid substitution to form a symmetrical amino acid sequence. The antibacterial activities and mechanisms of action of engineered peptides including KW-WK (KWRRWQWRRWK), FP-PF (FPRRWQWRRPF), FW-WF (FWRRWQWRRWF), and KK-KK (KKRRWQWRRKK) were investigated. The four engineered peptides could more effectively inhibit bacteria than the original peptide, LFcinB18–28. This suggested that a symmetrical amino acid sequence might enhance the antibacterial activity of AMPs. However, only peptides KW-WK, FP-PF, and KK-KK were safe; FW-WF displayed hemolytic activity. The engineered peptides shared cationic and amphipathic characteristics that facilitated interactions with the anionic microbial membranes, leading to disruption of membrane integrity and permeabilizing microbial membranes, resulting in cell death. Therefore, a symmetrical amino acid sequence and related structural parameters offer an alternative approach to the design of AMPs. This will provide a scientific basis for the design and synthesis of new AMPs.
Highlights
As multi-drug-resistant bacteria emerge, especially “superbugs,” antimicrobial peptides (AMPs) are increasingly recognized as a promising therapeutic alternative to conventional antibiotics [1]
Because of a unique bacteriostatic mechanism, it significantly reduces the likelihood of bacterial resistance [24]
The sequential template method means that a natural antimicrobial peptide can be studied by inserting selected amino acid in the peptide sequence to alter the net positive charge, in addition to other features, such as α-helices, hydrophilicity and hydrophobicity
Summary
As multi-drug-resistant bacteria emerge, especially “superbugs,” antimicrobial peptides (AMPs) are increasingly recognized as a promising therapeutic alternative to conventional antibiotics [1]. Numerous AMPs that act as components of the innate immune system have been isolated from living organisms [2]. Antibacterial peptides have many advantages compared to antibiotics, such as a broad antibacterial spectrum, good stability, minimal side effects, and minimal drug resistance Their principal mechanism of action involves binding to the conserved structural components of the bacterial envelope (e.g., lipopolysaccharide and lipoteichoic acid of Gram-negative and Gram-positive bacteria, respectively) [4].
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