Amino-terminated generation 2 poly(amidoamine)dendrimer as a potential broad-spectrum,non-inducing-resistance antibacterial agent
Treatment to septicemia caused by drug-resistant strains is a big challenge in clinic,as traditional antibiotics inevitably induce bacterial resistance,making it urgent to develop novel kinds of antibiotic drugs.Poly(amidoamine)(PAMAM)dendrimers are reported to have antibacterial activities.However,most studies focused on high generations(≥generation 3)of PAMAMs which exhibited high toxicities.The present study aimed at clarifying whether PAMAM could be used as a novel kind of antibacterial agents.We found that generation 2.0(G2.0)PAMAM-NH2 showed significant antibacterial effects against 15 out of 17 strains tested including 6 drug resistant strains,but had little toxicity to human GES-1 cells.Strikingly,G2.0 PAMAM-NH2(10-20 mg/kg)exhibited significant therapeutic effects against mice septicemia models induced by methicillin-resistant Staphylococcus aureus and Escherichia coli strains producing extended-spectrum beta lactamase,which increased the survival rates of infected mice from 0% to 40%-100%.Acute toxicity assays in BABL/c mice demonstrated that the median lethal dose of G2.0 PAMAM-NH2 was(84.04 + 21.72)mg/kg,much higher than that of therapeutic dose(10-20 mg/kg).Interestingly,G2.0 PAMAM-NH2 did not induce drug resistance after 15 successive subcultures.Scanning and transmission electron microscopy analysis suggested that G2.0 PAMAM-NH2 may inhibit the growth of bacteria by destroying the cell membranes.Thus,G2.0 PAMAM-NH2 are potential broad-spectrum and noninducing-resistance antibacterial agents.
PAMAM dendrimers Antibacterial activity Methicillin-resistant Staphylococcus aureus(MRSA) Escherichia coli(E.coli)strains producing extended-spectrum beta lactamase(ESBL) Toxicity
Xiaoyan Xue Xiaoxing Luo
Department of Pharmacology,School of Pharmacy,The Fourth Military Medical University,Xi”an,Shaanxi P Department of Pharmacology,School of Pharmacy,The Fourth Military Medical University,NO.169,Changle
国内会议
贵阳
英文
217-230
2012-07-01（万方平台首次上网日期，不代表论文的发表时间）