Multiplexed polypeptide-based hybrid bacterial clusters by tailoring the conjugation for synergistic treatment of infected wounds.

Drug-resistant bacterial infections and excessive inflammation pose serious challenges to wound healing. Currently, biomaterial-assisted antibacterial therapies demonstrate excellent therapeutic potential by enriching antibacterial agents at the site of infection and combining the advantages of multiple therapeutic agents. Here, inspired by bacterial aggregation behaviors in living organisms that regulate host physiological activities, a biomimetic polypeptide-based hybrid bacterial cluster is reported for treatment of infected wounds (PTS-UGT). Specifically, hybrid bacteria (UGT) were first constructed by a method of stepwise biological self-assembly with Staphylococcus epidermidis (SE) bacterial surface growth of gold and silver particles (UG) and polyphenolization of gold and silver particles. Subsequently, under the inducement of borate-diphenol coordination interactions and multiple hydrogen bonding, UGT was assembled with the side-chain boronic-acid-modified antibacterial polypeptide tobramycin (PTS) to form biomimetic hybrid bacterial clusters (PTS-UGT) by tailoring the conjugation methods. These clusters integrate the multiplexing and aggregation enhancement functions of bio-self-assembled gold, silver, polyphenol particles, bacterial immunomodulatory components and antibacterial polypeptides, which can effectively regulate the polarization of macrophages to M2 type and enhance the local effective drug concentration for multifunctional bacterial killing, thereby showing excellent antibacterial, anti-inflammatory and healing effects on infected wounds in mice, providing new ideas for the development of biomaterial-assisted antibacterial therapy.