Selective inactivation of Gram-positive bacteria in vitro and in vivo through metabolic labelling
Selective inactivation of Gram-positive bacteria in vitro and in vivo through metabolic labelling
复制标题
通过代谢标记在体外和体内选择性灭活革兰氏阳性菌
DOI：
10.1007/s40843-021-1735-0
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发表时间：
2021-08-18
影响因子：
8.1
通讯作者：
Huang, Wei
中科院分区：
文献类型：
--
作者：
Feng, Tao;Lu, Hui;Huang, Wei
Bacterial infections are grave threats to human health, particularly those caused by the most common Gram-positive bacteria. The massive administration of broad-spectrum antibiotics to treat various bacterial infections has led to the evolution and spread of drug resistance. As a universal antimicrobial technique unapt to induce drug resistance, photothermal therapy (PTT) is attracting extensive attention in recent years. However, its unspecific killing capability and side effects towards adjacent mammalian cells severely impede the practical applications. Herein, we proposed a metabolic engineering strategy to selectively inactivate Gram-positive bacteria by PTT. A bioorthogonal photothermal agent was prepared by the conjugation of IR-780 iodide and dibenzo-cyclooctyne (IR780-DBCO). Upon pre-metabolizing with 3-azido- D -alanine, Gram-positive bacteria rather than Gram-negative ones, such as Staphylococcus aureus and vancomycin-resistant Enterococcus faecalis (VRE), could be specifically tied up by the explosive IR780-DBCO via copper-free click chemistry. Thereafter, they spontaneously detonated under 15 min near-infrared light irradiation and inactivated nearly 100% Gram-positive bacteria in vitro. Moreover, superbug VRE-induced infection was significantly inhibited by this approach in a mouse skin wound model. 细菌感染, 尤其是最常见的革兰氏阳性菌引起的感染, 严重威胁着人类的生命健康. 抗生素是治疗细菌感染的首选药物, 但是它的大量使用造成了耐药性细菌的快速滋生和蔓延. 近年来, 光热抗菌疗法作为一种不易引起细菌耐药性的技术受到了广泛的关注. 然而, 非特异性的细菌杀伤和对邻近哺乳动物细胞的毒副作用严重限制了光热抗菌疗法的实际应用. 本文开发了一种代谢标记策略用于革兰氏阳性菌的选择性光热杀灭. 通过二苯并环辛炔(DBCO)和IR-780碘化物的共价连接,制备了生物正交的光热试剂IR780-DBCO. 革兰氏阳性菌或阴性菌经过3-叠氮基- D -丙氨酸预处理, 利用无铜点击化学反应实现了IR780-DBCO在金黄色葡萄球菌和耐万古霉素肠球菌等革兰氏阳性菌表面的选择性标记. 在15 min的近红外光照射下, 接近100%的革兰氏阳性菌被有效地杀灭. 此外, 该方法在小鼠皮肤伤口感染模型中也能够显著地抑制耐万古霉素肠球菌引起的感染. 我们提出的基于代谢标记的特异性光热杀灭革兰氏阳性菌的策略将会促进预临床研究中精准抗菌试剂的研发.