Wu Minghao, Li Yuting, Shen Huaxing, Zhang Yanan, Cong Wei, Hu Xiaochun, Shi Yejiao, Hu Honggang
Institute of Translational Medicine, Shanghai University, Shanghai, 200444, China.
School of Medicine, Shanghai University, Shanghai, 200444, China.
Adv Healthc Mater. 2024 Dec;13(31):e2402453. doi: 10.1002/adhm.202402453. Epub 2024 Aug 9.
Gram-positive S. aureus is one of the leading pathogens for death associated with antimicrobial resistance. The β-lactamase (Bla) secreted by methicillin-resistant S. aureus (MRSA) hydrolyzes nearly all β-lactam antibiotics, leaving only a few antibiotics available for the clinical treatment of MRSA infections. Thereby, a Bla-responsive peptide (BLAP) is designed here with the capacity of inhibiting MRSA infection through mimicking the host defense mechanism of human defensin-6. The BLAP comprising a self-assembling peptide sequence can respond specifically to the secreted Bla and assemble in situ surrounding MRSA. The assembled nanofibrous network is able to trap MRSA, preventing its invasion into the host cells effectively. As a consequence, the intramuscular injection of BLAP significantly restricted bacterial infection and abscess formation in mice. The biomimetic BLAP holds great potential for the efficient treatment of drug-resistant gram-positive bacterial infections.
革兰氏阳性金黄色葡萄球菌是与抗菌药物耐药性相关的主要致死病原体之一。耐甲氧西林金黄色葡萄球菌（MRSA）分泌的β-内酰胺酶（Bla）能水解几乎所有的β-内酰胺抗生素，使得临床上可用于治疗MRSA感染的抗生素寥寥无几。因此，在此设计了一种Bla响应肽（BLAP），它能够通过模拟人类防御素-6的宿主防御机制来抑制MRSA感染。包含自组装肽序列的BLAP能够特异性地响应分泌的Bla，并在MRSA周围原位组装。组装形成的纳米纤维网络能够捕获MRSA，有效防止其侵入宿主细胞。结果，肌肉注射BLAP可显著抑制小鼠体内的细菌感染和脓肿形成。这种仿生BLAP在有效治疗耐药革兰氏阳性细菌感染方面具有巨大潜力。
