Antimicrobial Microwebs of DNA-Histone Inspired from Neutrophil Extracellular Traps

• Type of Material: Article
• Authors: Yang Song, Emory University; Usha Kadiyala, University of Michigan; Priyan Weerappuli, University of Michigan; Jordan J. Valdez, Emory University; Srilakshmi Yalavarthi, University of Michigan; Cameron Louttit, University of Michigan; Jason S. Knight, University of Michigan; James J. Moon, University of Michigan; David Weiss, Emory University; J. Scott VanEpps, University of Michigan; Shuichi Takayama, Emory University
• Language: English
• Date: 2019-04-05
• Publisher: Wiley
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2019 John Wiley & Sons, Inc. All rights reserved
• Final Published Version (URL): http://dx.doi.org/10.1002/adma.201807436
• Title of Journal or Parent Work: Advanced Materials
• Volume: 31
• Issue: 14
• Start Page: e1807436
• End Page: e1807436
• Grant/Funding Information: This research project was funded by the National Institutes of Health (NIH NIAID U19 AI116482, R01 141883, & K08 AI128006; NIGMS R01 GM123517; NHLBI R01 HL134846; U01 CA210152), the VA (Merit award BX-002788), and a Burroughs Wellcome Fund Investigator in the Pathogenesis of Infectious Disease award.
• Keywords: Science & Technology - Other Topics; Nanoscience & Nanotechnology; Physics, Condensed Matter; Materials Science, Multidisciplinary; neutrophil extracellular traps; Atomic force; Chemistry, Physical; Technology; Immunity; Protect; bacteria E. coli; biomimetic materials; Chemistry, Multidisciplinary; antibiotic resistance; Chemistry; Escherichia-coli; DNA nanofiber networks; Materials Science; Physics; Science & Technology; Physics, Applied; Physical Sciences
• Research Categories: Biology, Microbiology; Health Sciences, Immunology; Engineering, Biomedical

Abstract

Neutrophil extracellular traps (NETs) are decondensed chromatin networks released by neutrophils that can trap and kill pathogens but can also paradoxically promote biofilms. The mechanism of NET functions remains ambiguous, at least in part, due to their complex and variable compositions. To unravel the antimicrobial performance of NETs, a minimalistic NET-like synthetic structure, termed “microwebs,” is produced by the sonochemical complexation of DNA and histone. The prepared microwebs have structural similarity to NETs at the nanometer to micrometer dimensions but with well-defined molecular compositions. Microwebs prepared with different DNA to histone ratios show that microwebs trap pathogenic Escherichia coli in a manner similar to NETs when the zeta potential of the microwebs is positive. The DNA nanofiber networks and the bactericidal histone constituting the microwebs inhibit the growth of E. coli. Moreover, microwebs work synergistically with colistin sulfate, a common and a last-resort antibiotic, by targeting the cell envelope of pathogenic bacteria. The synthesis of microwebs enables mechanistic studies not possible with NETs, and it opens new possibilities for constructing biomimetic bacterial microenvironments to better understand and predict physiological pathogen responses.