Anti-antimicrobial Peptides FOLDING-MEDIATED HOST DEFENSE ANTAGONISTS: FOLDING-MEDIATED HOST DEFENSE ANTAGONISTS

Lloyd Ryan, Baptiste Lamarre, Ting Diu, Jascindra Ravi, Peter J. Judge, Adam Temple, Matthew Carr, Eleonora Cerasoli, Bo Su, Howard F. Jenkinson, Glenn Martyna, Jason Crain, Anthony Watts, Maxim G. Ryadnov*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Antimicrobial or host defense peptides are innate immune regulators found in all multicellular organisms. Many of them fold into membrane-bound α-helices and function by causing cell wall disruption in microorganisms. Herein we probe the possibility and functional implications of antimicrobial antagonism mediated by complementary coiled-coil interactions between antimicrobial peptides and de novo designed antagonists: anti-antimicrobial peptides. Using sequences from native helical families such as cathelicidins, cecropins, and magainins we demonstrate that designed antagonists can co-fold with antimicrobial peptides into functionally inert helical oligomers. The properties and function of the resulting assemblies were studied in solution, membrane environments, and in bacterial culture by a combination of chiroptical and solid-state NMR spectroscopies, microscopy, bioassays, and molecular dynamics simulations. The findings offer a molecular rationale for anti-antimicrobial responses with potential implications for antimicrobial resistance.
Original languageEnglish
Pages (from-to)20162-20172
Number of pages11
JournalJournal of Biological Chemistry
Volume288
Issue number28
DOIs
Publication statusPublished - 12 Jul 2013

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