A polypeptide coating for preventing biofilm on implants by inhibiting antibiotic resistance genes

Danqing Liu; Yuejing Xi; Shunzhi Yu; Kexin Yang; Fan Zhang; Yuying Yang; Tianlong Wang; Shisheng He; Yunqing Zhu; Zhen Fan; Jianzhong Du

doi:10.1016/j.biomaterials.2022.121957

A polypeptide coating for preventing biofilm on implants by inhibiting antibiotic resistance genes

Biomaterials. 2023 Feb:293:121957. doi: 10.1016/j.biomaterials.2022.121957. Epub 2022 Dec 12.

Authors

Danqing Liu¹, Yuejing Xi², Shunzhi Yu³, Kexin Yang², Fan Zhang⁴, Yuying Yang², Tianlong Wang³, Shisheng He³, Yunqing Zhu⁵, Zhen Fan⁶, Jianzhong Du⁷

Affiliations

¹ Department of Orthopedics, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, 200072, China; Department of Polymeric Materials, School of Materials Science and Engineering, Tongji University, 4800 Caoan Road, Shanghai, 201804, China.
² Department of Polymeric Materials, School of Materials Science and Engineering, Tongji University, 4800 Caoan Road, Shanghai, 201804, China.
³ Department of Orthopedics, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, 200072, China.
⁴ Department of Oral Implantology, Stomatological Hospital and Dental School of Tongji University, Shanghai Research Center of Tooth Restoration and Regeneration, Shanghai, 200072, China.
⁵ Department of Orthopedics, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, 200072, China; Department of Polymeric Materials, School of Materials Science and Engineering, Tongji University, 4800 Caoan Road, Shanghai, 201804, China. Electronic address: 1019zhuyq@tongji.edu.cn.
⁶ Department of Orthopedics, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, 200072, China; Department of Polymeric Materials, School of Materials Science and Engineering, Tongji University, 4800 Caoan Road, Shanghai, 201804, China. Electronic address: fanzhen2018@tongji.edu.cn.
⁷ Department of Orthopedics, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, 200072, China; Department of Polymeric Materials, School of Materials Science and Engineering, Tongji University, 4800 Caoan Road, Shanghai, 201804, China. Electronic address: jzdu@tongji.edu.cn.

PMID: 36549042
DOI: 10.1016/j.biomaterials.2022.121957

Abstract

Aging population has been boosting the need for orthopedic implants. However, biofilm has been a major obstacle for orthopedic implants due to its insensitivity to antibiotics and tendency to drive antimicrobial resistance. Herein, an antibacterial polypeptide coating with excellent in vivo adhesive capacity was prepared to prevent implants from forming biofilms and inducing acquired antibiotic resistance. A peptide-based copolymer, poly[phenylalanine₁₀-stat-lysine₁₂]-block-3,4-dihydroxy-l-phenylalanine [Poly(Phe₁₀-stat-Lys₁₂)-DOPA] was modularly designed, where poly(Phe₁₀-stat-Lys₁₂) is antibacterial polypeptide with high antibacterial activity, and DOPA provides strong adhesion in both wet and dry microenvironments. Meanwhile, compared to traditional "graft-onto" methods, this antibacterial coating can be facilely achieved by immersing Titanium substrates into antibacterial polypeptide solution for 5 min at room temperature. The poly(Phe₁₀-stat-Lys₁₂)-DOPA polymer showed good antibacterial activity with minimum inhibitory concentrations against S. aureus and E. coli of 32 and 400 μg/mL, respectively. Compared to obvious antimicrobial resistance of S. aureus after continuous treatment with vancomycin, this antibacterial coating doesn't drive antimicrobial resistance upon long-term utilization. Transcriptome sequencing and qPCR tests further confirmed that the antibacterial coating was able to inhibit the expression of multiple peptide resistance factor (mprF) and lipoteichoic acid modification D-alanylation genes (dltB and dltC) that can increase the net positive charge of bacterial cell wall to induce the resistance to cationic antimicrobial peptides. In vivo experiments confirmed that this poly(Phe₁₀-stat-Lys₁₂)-DOPA coating can both effectively prevent biofilm formation through surface contact sterilization and avoid local and systemic infections. Overall, we proposed a facile method for preparing antibacterial orthopedic implants with longer indwelling time and without inducing antimicrobial resistance by coating a polypeptide-based polymer on the implants.

Keywords: Antibacterial; Antimicrobial resistance; Biofilm; Orthopedic implants; Polypeptides.

MeSH terms

Anti-Bacterial Agents* / pharmacology
Antimicrobial Cationic Peptides* / pharmacology
Biofilms* / drug effects
Coated Materials, Biocompatible* / pharmacology
Dihydroxyphenylalanine / pharmacology
Drug Resistance, Bacterial
Escherichia coli
Polymers / pharmacology
Prostheses and Implants / microbiology
Staphylococcus aureus / drug effects
Titanium* / pharmacology

Substances

Anti-Bacterial Agents
Antimicrobial Cationic Peptides
Coated Materials, Biocompatible
Dihydroxyphenylalanine
Polymers
Titanium