文章基本信息

标题：Anti-Psl Targeting of Pseudomonas aeruginosa Biofilms for Neutrophil-Mediated Disruption
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作者：Valerie A. Ray ; Preston J. Hill ; C. Kendall Stover 等
期刊名称：Scientific Reports
电子版ISSN：2045-2322
出版年度：2017
卷号：7
期号：1
页码：16065
DOI：10.1038/s41598-017-16215-6
语种：English
出版社：Springer Nature
摘要：Bacterial biofilms are recalcitrant to antibiotic therapy and a major cause of persistent and recurrent infections. New antibody-based therapies may offer potential to target biofilm specific components for host-cell mediated bacterial clearance. For Pseudomonas aeruginosa, human monoclonal antibodies (mAbs) targeting the Psl biofilm exopolysaccharide exhibit protective activity against planktonic bacteria in acute infection models. However, anti-Psl mAb activity against P. aeruginosa biofilms is unknown. Here, we demonstrate that anti-Psl mAbs targeting three distinct Psl epitopes exhibit stratified binding in mature in vitro biofilms and bind Psl within the context of a chronic biofilm infection. These mAbs also exhibit differential abilities to inhibit early biofilm events and reduce biomass from mature biofilms in the presence of neutrophils. Importantly, a mAb mixture with neutrophils exhibited the greatest biomass reduction, which was further enhanced when combined with meropenem, a common anti-Pseudomonal carbapenem antibiotic. Moreover, neutrophil-mediated killing of biofilm bacteria correlated with the evident mAb epitope stratification within the biofilm. Overall, our results suggest that anti-Psl mAbs might be promising candidates for adjunctive use with antibiotics to inhibit/disrupt P. aeruginosa biofilms as a result of chronic infection.