Lin Sisi, Xie Guocheng, He Jun, Meng Lu, Pang Yan, Liu Jinyao
State Key Laboratory of Systems Medicine for Cancer, Shanghai Cancer Institute, Shanghai Key Laboratory for Nucleic Acid Chemistry and Nanomedicine, Institute of Molecular Medicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
Shanghai Institute of Precision Medicine, Ninth People's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
Nat Biomed Eng. 2025 Feb 25. doi: 10.1038/s41551-025-01354-3.
The efficacy of bacteriophages in treating bacterial infections largely depends on the phages' vitality, which is impaired when they are naturally released from their hosts, as well as by culture media, manufacturing processes and other insults. Here, by wrapping phage-invaded bacteria individually with a polymeric nanoscale coating to preserve the microenvironment on phage-induced bacterial lysis, we show that, compared with naturally released phages, which have severely degraded proteins in their tail, the vitality of phages isolated from polymer-coated bacteria is maintained. Such latent phages could also be better amplified, and they more efficiently bound and lysed bacteria when clearing bacterial biofilms. In mice with bacterially induced enteritis and associated arthritis, latent phages released from orally administered bacteria coated with a polymer that dissolves at neutral pH had higher bioavailability and led to substantially better therapeutic outcomes than the administration of uncoated phages.
噬菌体在治疗细菌感染方面的功效很大程度上取决于噬菌体的活力，当它们从宿主中自然释放时，以及受到培养基、制造工艺和其他损害时，其活力会受到损害。在这里，通过用聚合物纳米涂层单独包裹被噬菌体侵染的细菌，以在噬菌体诱导的细菌裂解时保持微环境，我们发现，与尾部蛋白质严重降解的自然释放的噬菌体相比，从聚合物包裹的细菌中分离出的噬菌体的活力得以维持。这种潜伏噬菌体也能得到更好的扩增，并且在清除细菌生物膜时，它们能更有效地结合并裂解细菌。在患有细菌诱导性肠炎及相关关节炎的小鼠中，口服涂有在中性pH值下溶解的聚合物的细菌释放的潜伏噬菌体具有更高的生物利用度，并且与施用未包裹的噬菌体相比，能带来显著更好的治疗效果。
