Cationic Branched Polyethylenimine (BPEI) Disables Antibiotic Resistance in Methicillin‐Resistant Staphylococcus epidermidis (MRSE),ChemMedChem

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Cationic Branched Polyethylenimine (BPEI) Disables Antibiotic Resistance in Methicillin‐Resistant Staphylococcus epidermidis (MRSE)
ChemMedChem ( IF 3.6 ) 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

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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：

阳离子支化聚乙烯亚胺 (BPEI) 可消除耐甲氧西林表皮葡萄球菌 (MRSE) 的抗生素耐药性

表皮葡萄球菌是人类皮肤和粘膜上最常见的原核菌种之一，构成共生菌群。表皮葡萄球菌已成为原发性菌血症的最常见原因之一。感染很难诊断，因为病原体在人类皮肤上有天然的生态位，并且能够通过生物膜粘附在无生命的表面上。令人担忧的是，表皮葡萄球菌已经对许多抗生素产生了耐药性，这对人类健康构成了威胁。北美 MRSE 的大多数临床分离株被称为耐甲氧西林表皮葡萄球菌(MRSE)，主要由于mecA的存在而表现出 β-内酰胺耐药性，该基因以类似于甲氧西林耐药性的方式赋予 β-内酰胺抗生素耐药性金黄色葡萄球菌(MRSA)。 MecA编码青霉素结合蛋白 2a (PBP2a) 的表达，而表皮葡萄球菌的 β-内酰胺敏感菌株中不存在这种蛋白。我们可以使用 600 Da 支链聚乙烯亚胺 (BPEI) 禁用 MRSE 中的这一阻力因子。阳离子 BPEI 靶向阴离子壁磷壁酸 (WTA)，这是 PBP2a 正常发挥功能的重要辅助因子。我们发现 BPEI 可以协同 β-内酰胺类抗生素对抗 MRSE 的活性。生长曲线表明 BPEI 和苯唑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隔膜和细胞壁存在异常。因此，一线临床治疗与 BPEI 联合使用可以有效对抗 MRSE。

更新日期：2018-09-25

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