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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 non-inducing-resistance antibacterial agents.