Branched High Molecular Weight Glycopolypeptide With Broad-Spectrum Antimicrobial Activity for the Treatment of Biofilm Related Infections 机翻标题: 暂无翻译,请尝试点击翻译按钮。

来源
ACS applied materials & interfaces
年/卷/期
2018 / 10 / 1
页码
318-331
ISSN号
1944-8244
作者单位
Univ Palermo, Lab Biocompatible Polymers, Dept Sci & Tecnol Biol Chim & Farmaceut STEBICEF, Via Archirafi 32, I-90123 Palermo, Italy;Univ Palermo, Lab Biocompatible Polymers, Dept Sci & Tecnol Biol Chim & Farmaceut STEBICEF, Via Archirafi 32, I-90123 Palermo, Italy;Univ Palermo, Dept Sci & Tecnol Biol Chim & Farmaceut STEBICEF, Via Archirafi 32, I-90123 Palermo, Italy;Univ Palermo, Dept Sci Promoz Salute & Materno Infantile G DAle, Via Vespro 133, I-90127 Palermo, Italy;Univ Palermo, Dept Sci & Tecnol Biol Chim & Farmaceut STEBICEF, Via Archirafi 32, I-90123 Palermo, Italy;Univ Palermo, Dept Sci Promoz Salute & Materno Infantile G DAle, Via Vespro 133, I-90127 Palermo, Italy;Univ Palermo, Lab Biocompatible Polymers, Dept Sci & Tecnol Biol Chim & Farmaceut STEBICEF, Via Archirafi 32, I-90123 Palermo, Italy;Univ Palermo, Dept Sci Promoz Salute & Materno Infantile G DAle, Via Vespro 133, I-90127 Palermo, Italy;Univ Palermo, Lab Biocompatible Polymers, Dept Sci & Tecnol Biol Chim & Farmaceut STEBICEF, Via Archirafi 32, I-90123 Palermo, Italy;
作者
Mauro, Nicolo;Varvara, Paola;Cusimano, Maria Grazia;Geraci, Daniela Maria;Schillaci, Domenico;Giuffre, Mario;Cavallaro, Gennara;Maida, Carmelo Massimo;Giammona, Gaetano;
摘要
There are few therapeutic options to simultaneously tackle Staphylococcus aureus and Pseudomonas aeruginosa, two of the most relevant nosocomial and antibiotic-resistant pathogens responsible for implant, catheters and wound severe infections. The design and synthesis of polymers with inherent antimicrobial activity have gained increasing attention as a safe strategy to treat multi-drug-resistant microbes. Here, we tested the activity of a new. polymeric derivative with glycopolypeptide architecture (PAA-VC) bearing L-arginine, vancomycin, and colistin as side chains acting against multiple targets, which give rise to a broad spectrum antimicrobial activity favorably combining specific and nonspecific perturbation of the bacterial membrane. PAA-VC has been tested against planktonic and established biofilms of reference strains S. aureus ATCC 25923 and P. aeruginosa ATCC 15442 and susceptible or antibiotic resistant clinical isolates of the above-mentioned microorganisms. MIC values observed for the conjugate (48-190 and 95-190 nM for P. aeruginosa and S. aureus strains, respectively) showed higher efficacy if compared with the free vancomycin (MICs within 1.07-4.28 mu M) and colistin (MICs within 0.63-1.33 mu M). Additionally, being highly biocompatible (IC50 > 1000, 430, and 250 mu g mL(-1) for PAA-VC, vancomycin and colistin respectively) high-dosage can be adopted for the eradication of infections in patients. This positively influences the anti-biofilm activity of the conjugate leading to a quasi-total eradication of established clinically relevant biofilms (inhibition >90% at 500 mu g mL(-1)). We believe that the in vitro presented data, especially the activity against established biofilms of two relevant pathogens, the high biocompatibility and the good mucoadhesion properties, would allow the use of PAA-VC as promising candidate to successfully address emerging infections.
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关键词/主题词
antimicrobial polymers;synthetic polypeptides;colistin;vancomycin;Pseudomonas aeruginosa;Staphylococcus aureus;biofilms;
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