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Cationic Branched Polyethylenimine (BPEI) Disables Antibiotic Resistance in Methicillin‐Resistant Staphylococcus epidermidis (MRSE)
ChemMedChem ( IF 3.4 ) Pub Date : 2018-09-25 , DOI: 10.1002/cmdc.201800433
Anh K. Lam 1 , Melissa A. Hill 1 , Erika L. Moen 1 , Jennifer Pusavat 1 , Cassandra L. Wouters 1 , Charles V. Rice 1
Affiliation  

Staphylococcus epidermidis is one of the most prevalent prokaryotic species on human skin and mucosal membranes that constitute the commensal flora. S. epidermidis has become one of the most common causes of primary bacteremia. Infections are difficult to diagnose because the pathogen has natural niches on human skin and the ability to adhere to inanimate surfaces via biofilms. Alarmingly, S. epidermidis has acquired resistance to many antibiotics, which presents a danger to human health. Known as methicillin‐resistant S. epidermidis (MRSE), most clinical isolates of MRSE in North America exhibit β‐lactam resistance primarily due to the presence of mecA, a gene that bestows β‐lactam antibiotic resistance in a manner similar to methicillin‐resistant Staphylococcus aureus (MRSA). MecA encodes for expression of penicillin‐binding protein 2a (PBP2a), which is absent in β‐lactam susceptible strains of S. epidermidis. We can disable this resistance factor in MRSE with 600‐Da branched polyethylenimine (BPEI). Cationic BPEI targets anionic wall teichoic acid (WTA), an essential cofactor for proper functioning of PBP2a. We found that BPEI synergizes the activity of β‐lactam antibiotics against MRSE. Growth curves suggest that the combination of BPEI and oxacillin is bactericidal. Electron micrographs indicate abnormalities in the cellular septa and cell walls of treated samples. Therefore, first‐line clinical treatments can be effective against MRSE when used in combination with BPEI.

中文翻译:

阳离子支链聚乙烯亚胺(BPEI)禁用耐甲氧西林表皮葡萄球菌(MRSE)的抗生素耐药性

表皮葡萄球菌是构成共生菌群的人皮肤和粘膜上最普遍的原核物种之一。表皮葡萄球菌已成为原发菌血症的最常见原因之一。感染难以诊断,因为病原体在人的皮肤上具有天然的壁ches,并且能够通过生物膜粘附至无生命的表面。令人震惊的是,表皮葡萄球菌已获得对许多抗生素的抗性,这对人类健康构成了危险。被称为耐甲氧西林的表皮葡萄球菌(MRSE),在北美,大多数MRSE临床分离株表现出对β-内酰胺的耐药性,主要是由于存在mecA,以类似于耐甲氧西林的金黄色葡萄球菌(MRSA)的方式赋予β-内酰胺类抗生素抗性的基因。MecA编码表达青霉素结合蛋白2a(PBP2a),在表皮葡萄球菌对β-内酰胺的敏感菌株中不存在。我们可以使用600-Da支链聚乙烯亚胺(BPEI)禁用MRSE中的这种抗性因子。阳离子BPEI靶向阴离子壁板壁酸(WTA),它是PBP2a正常运行的重要辅助因子。我们发现BPEI可以增强β-内酰胺类抗生素对MRSE的活性。生长曲线表明BPEI和奥沙西林的组合具有杀菌作用。电子显微照片表明处理样品的细胞间隔和细胞壁异常。因此,与BPEI结合使用时,一线临床治疗可以有效抵抗MRSE。
更新日期:2018-09-25
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