Abstract
The continued emergence of new antibiotic resistant bacterial strains has resulted in great interest in the development of new antimicrobial treatments. Antimicrobial peptides (AMPs) are one of many potential classes of molecules to help meet this emerging need. AMPs are naturally derived sequences, which act as part of the innate immune system of organisms ranging from insects through humans. We investigated the antimicrobial peptide AP3, which is originally isolated from the winter flounder Pleuronectes americanus. This peptide is of specific interest because it does not exhibit the canonical facially amphiphilic orientation of side chains when in a helical orientation. Different analogs of AP3 were synthesized in which length, charge identity, and Trp position were varied to investigate the sequence-structure and activity relationship. We performed biophysical and microbiological characterization using fluorescence spectroscopy, CD spectroscopy, vesicle leakage assays, bacterial membrane permeabilization assays, and minimal inhibitory concentration (MIC) assays. Fluorescence spectroscopy showed that the peptides bind to lipid bilayers to similar extents, while CD spectra show the peptides adopt helical conformations. All five peptides tested in this study exhibited binding to model lipid membranes, while the truncated peptides showed no measurable antimicrobial activity. The most active peptide proved to be the parent peptide AP3 with the highest degree of leakage and bacterial membrane permeabilization. Moreover, it was found that the ability to permeabilize model and bacterial membranes correlated most closely with the ability to predict antimicrobial activity.
Highlights
Antimicrobial peptides (AMPs) are biomolecules conserved through evolution and found in all complex living organisms [1,2]
It was found that the ability to permeabilize model and bacterial membranes correlated most closely with the ability to predict antimicrobial activity
Bacteria were exposed to AMPs throughout millions of years of evolution, yet there has not been any significant development of resistance [8]
Summary
Antimicrobial peptides (AMPs) are biomolecules conserved through evolution and found in all complex living organisms [1,2]. One of the most well-studied classes are those which are ribosomally synthesized as part of the natural host defense mechanism [3]. They are widely used as a defense mechanism among multicellular organisms and are often produced to play an important role in innate immune systems and the host defense mechanism [4,5,6,7]. Bacteria were exposed to AMPs throughout millions of years of evolution, yet there has not been any significant development of resistance [8]. This low propensity for resistance and ability to kill or inhibit bacterial growth has made AMPs an ideal target for new drug discovery to help combat antibiotic resistant bacteria [1,8]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
