Engineering Short Antimicrobial Peptides to Specifically Target Fusobacterium nucleatum in the Mixed Microbial Population

Liu, Zhao; Wang, Yijie; Zhang, Chen; Yang, Yongshuai; Zhang, Junfeng

2024-06-01

10.1021/acsinfecdis.4c00387

ACS INFECTIOUS DISEASES   影响因子和分区

2373-8227

Antimicrobial peptides (AMPs) are becoming next-generation alternative antibacterial agents because of the rapid increase in resistance in bacteria against existing antibiotics, which can also be attributed to the formation of resilient biofilms. However, their widespread use is limited because of their poor absorption, higher dosage requirements, and delayed onset of the bioactivity to elicit a desired response. Here we developed a short AMP that specifically targeted Fusobacterium nucleatum. We conjugated 23R to a statherin-derived peptide (SDP) through rational design; this conjugate binds to FomA, a major porin protein of F. nucleatum. The SDP-tagged 23R exhibited rapid and highly specific bactericidal efficacy against F. nucleatum. Further, IC50 values were in the nanomolar range, and they were 100-fold lower than those obtained with unconjugated 23R. In a human gut microbiota model, 0.1 nM SDP-23R achieved 99% clearance of F. nucleatum ATCC 25586 without markedly altering resident microbiota. Here we demonstrated that binding-peptide-coupled AMPs show increased killing efficacy and specificity for the target pathogen without affecting the resident microbiota.

antimicrobial peptide Fusobacterium nucleatum peptide engineering targeted antibacterial therapy anti-biofilm

SCI

英语

第一 ; 通讯

Shenzhen Special Fund for Innovation and Entrepreneurship of Overseas High-Level Talents Peacock Team[KQTD20170810111314625] ; Shenzhen Institutes of Advanced Technology External Funds[DWKF20190001] ; National Natural Science Foundation of China's Research Fund for International Young Scientists[22050410270] ; Guangdong Innovative and Entrepreneurial Research Team Program[2019ZT08Y191]

Pharmacology & Pharmacy ; Infectious Diseases

Chemistry, Medicinal ; Infectious Diseases

WOS:001255674800001

AMER CHEMICAL SOC

Web of Science

Southern Univ Sci & Technol SUSTech, Dept Biomed Engn, Shenzhen 518055, Peoples R China

Liu, Zhao,Wang, Yijie,Zhang, Chen,et al. Engineering Short Antimicrobial Peptides to Specifically Target Fusobacterium nucleatum in the Mixed Microbial Population[J]. ACS INFECTIOUS DISEASES,2024.

Liu, Zhao,Wang, Yijie,Zhang, Chen,Yang, Yongshuai,&Zhang, Junfeng.(2024).Engineering Short Antimicrobial Peptides to Specifically Target Fusobacterium nucleatum in the Mixed Microbial Population.ACS INFECTIOUS DISEASES.

Liu, Zhao,et al."Engineering Short Antimicrobial Peptides to Specifically Target Fusobacterium nucleatum in the Mixed Microbial Population".ACS INFECTIOUS DISEASES (2024).