Synergy between Winter Flounder antimicrobial peptides

Author:

Clarke MariaORCID,Hind Charlotte K.,Ferguson Philip M.,Manzo Giorgia,Mistry Bhumil,Yue Bingkun,Romanopulos Janis,Clifford Melanie,Bui Tam T.,Drake Alex F.,Lorenz Christian D.ORCID,Sutton J. Mark,Mason A. JamesORCID

Abstract

AbstractSome antimicrobial peptides (AMPs) have potent bactericidal activity and are being considered as potential alternatives to classical antibiotics. In response to an infection, such AMPs are often produced in animals alongside other peptides with low or no perceivable antimicrobial activity, whose role is unclear. Here we show that six AMPs from the Winter Flounder (WF) act in synergy against a range of bacterial pathogens and provide mechanistic insights into how this increases the cooperativity of the dose-dependent bactericidal activity and potency that enable therapy. Only two WF AMPs have potent antimicrobial activity when used alone but we find a series of two-way combinations, involving peptides which otherwise have low or no activity, yield potent antimicrobial activity. Weakly active WF AMPs modulate the membrane interactions of the more potent WF AMPs and enable therapy in a model of Acinetobacter baumannii burn wound infection. The observed synergy and emergent behaviour may explain the evolutionary benefits of producing a family of related peptides and are attractive properties to consider when developing AMPs towards clinical applications.

Funder

RCUK | Engineering and Physical Sciences Research Council

National Centre for the Replacement Refinement and Reduction of Animals in Research

RCUK | Biotechnology and Biological Sciences Research Council

DH | National Institute for Health Research

Maudsley Charity

Guy’s and St Thomas’ Charity

Public Health England

Publisher

Springer Science and Business Media LLC

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