Department of Prosthodontics, Peking University School and Hospital of Stomatology & National Center of Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Research Center of Oral Biomaterials and Digital Medical Devices & Beijing Key Laboratory of Digital Stomatology & Research Center of Engineering and Technology for Computerized Dentistry Ministry of Health & NMPA Key Laboratory for Dental Materials, Beijing 100081, China.
Department of Geriatric Dentistry, Beijing Laboratory of Biomedical Materials, Peking University School and Hospital of Stomatology, Beijing 100081, China.
Nano Lett. 2022 Oct 26;22(20):8294-8303. doi: 10.1021/acs.nanolett.2c03160. Epub 2022 Oct 14.
Microbial resistance to antibiotics is one of the greatest global healthcare challenges. There is an urgent need to develop effective strategies to overcome antimicrobial resistance. We, herein, report photoinduced in situ growth of a cationic polymer from the -terminus of lysozyme. The attachment of the cationic polymer improves the proteolytic and thermal stability of lysozyme. Notably, the conjugate can efficiently overcome lysozyme resistance in Gram-positive bacteria and antibiotics-resistance in Gram-negative bacteria, which may be ascribed to the synergistic interactions of lysozyme and the cationic polymer with the bacteria to disrupt their cell membranes. In a rat periodontitis model, the lysozyme-polymer conjugate not only greatly outperforms lysozyme in therapeutic efficacy but also is superior to minocycline hydrochloride, which is the gold standard for periodontitis therapy. These findings may provide an efficient strategy to dramatically enhance the antimicrobial activities of lysozyme and pave a way to overcome antimicrobial resistance.
微生物对抗生素的耐药性是全球医疗保健面临的最大挑战之一。迫切需要开发有效的策略来克服抗微生物药物耐药性。我们在此报告了一种从溶菌酶的 -末端原位诱导阳离子聚合物生长的方法。阳离子聚合物的附着提高了溶菌酶的蛋白水解和热稳定性。值得注意的是，该缀合物可以有效地克服革兰氏阳性菌中的溶菌酶耐药性和革兰氏阴性菌中的抗生素耐药性，这可能归因于溶菌酶和阳离子聚合物与细菌的协同相互作用，以破坏它们的细胞膜。在大鼠牙周炎模型中，溶菌酶-聚合物缀合物不仅在治疗效果上大大优于溶菌酶，而且优于米诺环素盐酸盐，米诺环素盐酸盐是牙周炎治疗的金标准。这些发现可能为显著提高溶菌酶的抗菌活性提供了一种有效的策略，并为克服抗微生物药物耐药性铺平了道路。
