Destabilization of α-Helical Structure in Solution Improves Bactericidal Activity of Antimicrobial Peptides: Opposite Effects on Bacterial and Viral Targets

Antimicrobial Agents and Chemotherapy
David O UlaetoKonrad Beck

Abstract

We have previously examined the mechanism of antimicrobial peptides on the outer membrane of vaccinia virus. We show here that the formulation of peptides LL37 and magainin-2B amide in polysorbate 20 (Tween 20) results in greater reductions in virus titer than formulation without detergent, and the effect is replicated by substitution of polysorbate 20 with high-ionic-strength buffer. In contrast, formulation with polysorbate 20 or high-ionic-strength buffer has the opposite effect on bactericidal activity of both peptides, resulting in lesser reductions in titer for both Gram-positive and Gram-negative bacteria. Circular dichroism spectroscopy shows that the differential action of polysorbate 20 and salt on the virucidal and bactericidal activities correlates with the α-helical content of peptide secondary structure in solution, suggesting that the virucidal and bactericidal activities are mediated through distinct mechanisms. The correlation of a defined structural feature with differential activity against a host-derived viral membrane and the membranes of both Gram-positive and Gram-negative bacteria suggests that the overall helical content in solution under physiological conditions is an important feature for consideratio...Continue Reading

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Citations

Mar 21, 2018·Journal of Biomolecular Structure & Dynamics·P PetkovL Litov
Jun 26, 2020·Frontiers in Microbiology·Céline ChessaMagali Garcia
Aug 4, 2019·Viruses·Aslaa AhmedAarthi Narayanan
Aug 7, 2019·Current Medicinal Chemistry·David C Brice, Gill Diamond
Aug 1, 2020·Frontiers in Cellular and Infection Microbiology·Derry K MercerAlfredo M Angeles-Boza
Jan 28, 2021·The Journal of Antimicrobial Chemotherapy·Mário R FelícioSónia Gonçalves
Jun 3, 2021·Antibiotics·Kylen E Ridyard, Joerg Overhage

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Methods Mentioned

BETA
circular dichroism

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