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针对多重耐药微生物的超分子阳离子组装体:活性及作用机制

Supramolecular cationic assemblies against multidrug-resistant microorganisms: activity and mechanism of action.

作者信息

Carrasco Letícia Dias de Melo, Sampaio Jorge Luiz Mello, Carmona-Ribeiro Ana Maria

机构信息

Departamento de Bioquímica, Instituto de Química, Universidade de São Paulo, Caixa Postal 26077, CEP 05513-970 São Paulo, Brazil.

Departamento de Análises Clínicas e Toxicológicas, Faculdade de Ciências Farmacêuticas, Universidade de São Paulo, CEP 05508-900 São Paulo, Brazil.

出版信息

Int J Mol Sci. 2015 Mar 19;16(3):6337-52. doi: 10.3390/ijms16036337.

Abstract

The growing challenge of antimicrobial resistance to antibiotics requires novel synthetic drugs or new formulations for old drugs. Here, cationic nanostructured particles (NPs) self-assembled from cationic bilayer fragments and polyelectrolytes are tested against four multidrug-resistant (MDR) strains of clinical importance. The non-hemolytic poly(diallyldimethylammonium) chloride (PDDA) polymer as the outer NP layer shows a remarkable activity against these organisms. The mechanism of cell death involves bacterial membrane lysis as determined from the leakage of inner phosphorylated compounds and possibly disassembly of the NP with the appearance of multilayered fibers made of the NP components and the biopolymers withdrawn from the cell wall. The NPs display broad-spectrum activity against MDR microorganisms, including Gram-negative and Gram-positive bacteria and yeast.

摘要

抗生素抗微生物耐药性带来的挑战日益严峻,这需要新型合成药物或旧药的新配方。在此,由阳离子双层片段和聚电解质自组装而成的阳离子纳米结构颗粒(NPs)针对四种具有临床重要性的多重耐药(MDR)菌株进行了测试。作为NP外层的非溶血聚二烯丙基二甲基氯化铵(PDDA)聚合物对这些微生物表现出显著活性。细胞死亡机制涉及细菌膜裂解,这是通过内部磷酸化化合物的泄漏确定的,并且随着由NP成分和从细胞壁中提取的生物聚合物制成的多层纤维的出现,NP可能会解体。这些NP对MDR微生物具有广谱活性,包括革兰氏阴性菌、革兰氏阳性菌和酵母。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4bbc/4394535/f111c9e9d58f/ijms-16-06337-g001.jpg

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