Dosage-dependent antimicrobial activity of DNA-histone microwebs against Staphylococcus aureus

DNA-组蛋白微网对金黄色葡萄球菌的剂量依赖性抗菌活性

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作者:Ting Yang, Shi Yang, Tasdiq Ahmed, Katherine Nguyen, Jinlong Yu, Xuejun Cao, Rui Zan, Xiaonong Zhang, Hao Shen, Meredith E Fay, Evelyn Kendall Williams, Wilbur A Lam, J Scott VanEpps, Shuichi Takayama, Yang Song

Abstract

Neutrophil extracellular traps (NETs) is an antimicrobial cobweb-structured material produced by immune cells for clearance of pathogens in the body, but paradoxically associated with biofilm formation and exacerbated lung infections. To provide a better materials perspective on the pleiotropic roles played by NETs at diverse compositions/concentrations, a NETs-like material (called 'microwebs', abbreviated as μwebs) is synthesized for decoding the antimicrobial activity of NETs against Staphylococcus aureus in infection-relevant conditions. We show that μwebs composed of low-to-intermediate concentrations of DNA-histone complexes successfully trap and inhibit S. aureus growth and biofilm formation. However, with growing concentrations and histone proportions, the resulting microwebs appear gel-like structures accompanied by reduced antimicrobial activity that can even promote formation of S. aureus biofilms. Our simplified model of NETs provides a materials-based evidence on NETs-relevant pathology in the development of biofilms.

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