■多重耐药肺炎克雷伯菌的出现(K.肺炎)和有效抗生素的下降导致迫切需要新的抗菌剂。本研究的目的是研究抗菌肽对庆大霉素耐药(RT)肺炎克雷伯菌的治疗作用,并筛选有效的抗菌肽。
■在这项研究中,用梯度庆大霉素诱导RT菌株,并通过检测外排泵基因的表达水平选择RT菌株,孔蛋白基因,和菌株的生物膜形成基因以及它们对细胞的影响。然后研究了四种抗菌肽对外排泵活性的影响,检测感染后的生物膜形成水平和细胞状况,探讨抗菌肽对RT菌株的影响。最后,RT菌株用于诱导小鼠肺炎模型,四种抗菌肽用于治疗肺炎小鼠进行体内实验。检测各组肺组织的病理变化,探讨抗菌肽对RT株体内作用最显著的抗菌肽。
■结果表明,RT菌株(菌株C和菌株I)的最小抑制浓度显着高于野生型菌株,和外排泵的表达式,孔蛋白和生物膜形成基因显著增加。抗菌肽能有效抑制RT菌株的生物膜形成和外排泵蛋白功能。此外,抗菌肽在体外和体内均显示出有希望的抗菌作用。
■本研究为抗菌肽治疗庆大霉素耐药肺炎克雷伯菌感染提供了理论依据,发现KLA明显优于LL37,马加宁I,KLA和Dermaseptin(细胞中10μg/mL,小鼠中50μg)。
UNASSIGNED: The emergence of multidrug-resistant Klebsiella pneumoniae (K. pneumoniae) and the decline of effective antibiotics lead to the urgent need for new antibacterial agents. The aim of this study is to investigate the therapeutic effect of antimicrobial peptides against gentamicin-resistant (RT) K. pneumoniae and to screen effective antimicrobial peptides.
UNASSIGNED: In this study, the RT strains were induced by gradient gentamicin, and the RT strains were selected by detecting the expression levels of efflux pump genes, porin genes, and biofilm formation genes of the strains combined with their effects on the cells. Then the effects of four antimicrobial peptides on the efflux pump activity, biofilm formation level and cell condition after infection were detected to explore the effects of antimicrobial peptides on RT strains. Finally, the RT strain was used to induce a mouse model of pneumonia, and the four antimicrobial peptides were used to treat pneumonia mice for in vivo experiments. The pathological changes in lung tissues in each group were detected to explore the antimicrobial peptide with the most significant effect on the RT strain in vivo.
UNASSIGNED: The results showed that the minimal inhibitory concentrations of the RT strains (strain C and strain I) were significantly higher than those of the wild-type strain, and the expression of efflux pump, porin and biofilm formation genes was significantly increased. The antimicrobial peptides could effectively inhibit the biofilm formation and efflux pump protein function of the RT strains. In addition, the antimicrobial peptides showed promising antibacterial effects both in vitro and in vivo.
UNASSIGNED: Our study provided a theoretical basis for the treatment of gentamicin resistant K. pneumoniae infection with antimicrobial peptides, and found that KLA was significantly superior to LL37, Magainin I, KLA and Dermaseptin (10 μg/mL in cells, 50 μg in mice).