Monoclonal antibodies against DNA-binding tips of DNABII proteins disrupt biofilms in vitro and induce bacterial clearance in vivo

被引:75
作者
Novotny, Laura A.
Jurcisek, Joseph A.
Goodman, Steven D.
Bakaletz, Lauren O.
机构
[1] Nationwide Childrens Hosp, Res Inst, Ctr Microbial Pathogenesis, 700 Childrens Dr, Columbus, OH 43205 USA
[2] Ohio State Univ, Coll Med, Dept Pediat, 700 Childrens Dr, Columbus, OH 43205 USA
来源
EBIOMEDICINE | 2016年 / 10卷
关键词
Integration host factor (IHF); Histone like protein (HU); Nontypeable Haemophilus influenzae; Pseudomonas aeruginosa; Otitis media; Respiratory tract infection; INTEGRATION HOST FACTOR; PSEUDOMONAS-AERUGINOSA; OTITIS-MEDIA; MICROBIOLOGY; RESOLUTION; DISEASE; IHF;
D O I
10.1016/j.ebiom.2016.06.022
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
The vast majority of chronic and recurrent bacterial diseases are attributed to the presence of a recalcitrant bio-film that contributes significantly to pathogenesis. As such, these diseases will require an innovative therapeutic approach. We targeted DNABII proteins, an integral component of extracellular DNA (eDNA) which is universally found as part of the pathogenic biofilm matrix to develop a biofilm disrupting therapeutic. We show that a cocktail of monoclonal antibodies directed against specific epitopes of a DNABII protein is highly effective to disrupt diverse biofilms in vitro as well as resolve experimental infection in vivo, in both a chinchilla and murine model. Combining this monoclonal antibody cocktail with a traditional antibiotic to kill bacteria newly released from the biofilm due to the action of the antibody cocktail was highly effective. Our results strongly support these monoclonal antibodies as attractive candidates for lead optimization as a therapeutic for resolution of bacterial biofilm diseases. (C) 2016 The Authors. Published by Elsevier B.V.
引用
收藏
页码:33 / 44
页数:12
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