Abstract
Drug-resistant bacteria infections and drug residues have been increasing and causing antibiotic resistance and public health threats worldwide. Antimicrobial peptides (AMPs) are novel antimicrobial drugs with the potential to solve these problems. Here, a peptide based on our previously studied peptide PMAP-36PW was designed via N-terminal myristoylation and referred to as Myr-36PW. The fatty acid modification provided the as-prepared peptide with good stability and higher antimicrobial activity compared with PMAP-36PW in vitro. Moreover, Myr-36PW exhibited effective anti-biofilm activity against Gram-negative bacteria and may kill bacteria by improving the permeability of their membranes. In addition, the designed peptide Myr-36PW could inhibit the bacterial growth of Staphylococcus aureus ATCC 25923 and Pseudomonas aeruginosa GIM 1.551 to target organs, decrease the inflammatory damage, show an impressive therapeutic effect on mouse pneumonia and peritonitis experiments, and promote abscess reduction and wound healing in infected mice. These results reveal that Myr-36PW is a promising antimicrobial agent against bacterial infections.
Highlights
Traditional antibiotic resistance and veterinary drug residues have been annually increasing and causing a serious global public health threat (CiŽman and Plankar Srovin, 2018)
Myr-36PW was designed through fatty acid modification to further improve the antibacterial activity of PMAP-36PW
PMAP36PW still has some shortcomings: The antimicrobial activity of PMAP-36PW on Gram-negative bacteria was worse than that on Gram-positive bacteria, and PMAP-36PW showed no antimicrobial activity against Enterococcus faecium B21
Summary
Traditional antibiotic resistance and veterinary drug residues have been annually increasing and causing a serious global public health threat (CiŽman and Plankar Srovin, 2018). The World Health Organization (WHO) has emphasized that the incidence of infections caused by drug-resistant bacteria has been increasing globally and may kill 10 million people by 2050 (Woolhouse et al, 2016; Zhen et al, 2019). Only few AMPs are currently in clinical application due to their instability, high cytotoxicity and low antimicrobial activity (Greber and Dawgul, 2016; Jacob et al, 2016). Many methods such as substitution (Zhou et al, 2019a), cyclization (Mwangi et al, 2019b), and hybridization (Miao et al, 2020) have been studied and adopted to overcome these shortcomings.
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