关键词: A20L Klebsiella pneumoniae antibacterial antibiofilm antimicrobial peptide carbapenem-resistance

Mesh : Klebsiella pneumoniae / drug effects Biofilms / drug effects Animals Mice Anti-Bacterial Agents / pharmacology Klebsiella Infections / drug therapy Microbial Sensitivity Tests Carbapenems / pharmacology RAW 264.7 Cells Antimicrobial Peptides / pharmacology chemistry Moths / drug effects microbiology Carbapenem-Resistant Enterobacteriaceae / drug effects Antimicrobial Cationic Peptides / pharmacology

来  源:   DOI:10.1128/spectrum.03979-23   PDF(Pubmed)

Abstract:
Antimicrobial resistance has become a growing public health threat in recent years. Klebsiella pneumoniae is one of the priority pathogens listed by the World Health Organization. Antimicrobial peptides are considered promising alternatives to antibiotics due to their broad-spectrum antibacterial activity and low resistance. In this study, we investigated the antibacterial activity of antimicrobial peptide A20L against K. pneumoniae. In vitro antibacterial activity of A20L against K. pneumoniae was demonstrated by broth microdilution method. We confirmed the in vivo efficacy of A20L by Galleria mellonella infection model. In addition, we found that A20L also had certain antibiofilm activity by crystal violet staining. We also evaluated the safety and stability of A20L, and the results revealed that at a concentration of ≤128 µg/mL, A20L exhibited negligible toxicity to RAW264.7 cells and no substantial toxicity to G. mellonella. A20L was stable at different temperatures and with low concentration of serum [5% fetal bovine serum (FBS)]; however, Ca2+, Mg2+, and high serum concentrations reduced the antibacterial activity of A20L. Scanning electron microscope (SEM) and membrane permeability tests revealed that A20L may exhibit antibacterial action by damaging bacterial cell membranes and increasing the permeability of outer membrane. Taken together, our results suggest that A20L has significant development potential as a therapeutic antibiotic alternative, which provides ideas for the treatment of K. pneumoniae infection.
OBJECTIVE: A20L showed antibacterial and anti-infective efficacy in vitro and in vivo against Klebsiella pneumoniae. It can have an antibacterial effect by disrupting the integrity of cell membranes. A20L displayed anti-biofilm and anti-inflammatory activity against carbapenem-resistant K. pneumoniae and certain application potential in vivo, which provides a new idea for the clinical treatment of biofilm-associated infections.
摘要:
近年来,抗菌素耐药性已成为日益严重的公共卫生威胁。肺炎克雷伯菌是世界卫生组织列出的重点致病菌之一。抗菌肽由于其广谱抗菌活性和低抗性而被认为是抗生素的有希望的替代品。在这项研究中,我们研究了抗菌肽A20L对肺炎克雷伯菌的抗菌活性。通过肉汤微量稀释法证明了A20L对肺炎克雷伯菌的体外抗菌活性。我们通过Galleriamellonella感染模型证实了A20L的体内功效。此外,通过结晶紫染色,我们发现A20L也具有一定的抗生物膜活性。我们还评估了A20L的安全性和稳定性,结果表明,在≤128µg/mL的浓度下,A20L对RAW264.7细胞表现出可忽略的毒性,并且对梅洛氏杆菌没有实质毒性。A20L在不同温度和低浓度血清[5%胎牛血清(FBS)]下是稳定的;然而,Ca2+,Mg2+,高血清浓度降低了A20L的抗菌活性。扫描电子显微镜(SEM)和膜通透性测试显示,A20L可能通过破坏细菌细胞膜并增加外膜的通透性而表现出抗菌作用。一起来看,我们的结果表明,A20L作为治疗性抗生素替代品具有巨大的发展潜力,为肺炎克雷伯菌感染的治疗提供了思路。
目的:A20L对肺炎克雷伯菌具有体内外抗菌和抗感染作用。它可以通过破坏细胞膜的完整性而具有抗菌作用。A20L对耐碳青霉烯类肺炎克雷伯菌具有抗生物膜和抗炎活性,在体内具有一定的应用潜力,为临床治疗生物膜相关感染提供了新的思路。
公众号