A Sustained-Release Depot of Thermosensitive Polypeptide Fused Glycosidase Synergizes with Vancomycin to Eradicate...

Biomedical implants have revolutionized medicine, but they increase the risk of infection. The treatment of implant infection is tricky because bacterial biofilms performed on the implants are difficult to remove, and bacteria in the biofilm have high resistance and tolerance to antibiotics. Herein, we report a sustained release depot of a thermosensitive glycoside hydrolase of ELP-DspB, in which dispersin B (DspB) is genetically fused to a thermosensitive elastin-like polypeptide (ELP), to efficiently degrade bacterial biofilms and thus overcome antibiotic resistance. ELP-DspB possesses the antibiofilm bioactivity of DspB to synergize with antibiotics as well as the thermosensitivity of ELP. Moreover, it not only improves the stability of DspB but also diminishes the immunogenicity of DspB. In a mouse model of implant infection by methicillin resistant Staphylococcus epidermidis (MRSE), the thermosensitivity of ELP-DspB enabled the formation of a one-month sustained-release drug reservoir upon topical administration near the MRSE biofilm-infected implant. In combination with antibiotics, a single subcutaneous injection of ELP-DspB efficiently eradicated implant infections without detectable side effects, which was not achieved by DspB. Generally, the ELP fusion is a promising strategy to improve the efficacy of glycoside hydrolases in synergy with antibiotics in eradicating biofilm-related implant infections.