A synthetic cyclized antimicrobial peptide with potent effects against drug resistant skin pathogens

John Kerr  White; Soumitra  Mohanty; Taj Muhammad; Magdalena  de Arriba Sanchez de la Campa; Wael E Houssen; Natalia  Ferraz; Ulf Göransson; Annelie  Brauner

A synthetic cyclized antimicrobial peptide with potent effects against drug resistant skin pathogens

John Kerr White, Soumitra Mohanty, Taj Muhammad, Magdalena de Arriba Sanchez de la Campa, Wael E Houssen, Natalia Ferraz, Ulf Göransson, Annelie Brauner^* (Corresponding Author)

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

Abstract

Dermal infections requiring treatment are usually treated with conventional
antibiotics, but the rise of bacterial resistance to first-line antibiotics warrants alternative therapeutics. Here, we report that a backbone-cyclized antimicrobial peptide, CD4-PP, designed from the human host defence peptide LL-37, has strong direct antibacterial effects on antibiotic sensitive as well as resistant type strains and clinical isolates of common skin pathogens in low (and treatment with CD4-PP is able to clear bacterial infections in infected keratinocytes.
Additionally, CD4-PP treatment significantly reduces the wound area in a lawn of
keratinocytes infected with MRSA. In conclusion, CD4-PP has the potential to serve as a future drug treating wounds infected with antibiotic resistant bacteria.

Original language	English
Journal	ACS Infectious Diseases
Publication status	Accepted/In press - 19 Apr 2023

Keywords

Keratinocytes;
MRSA
synthetic antimicrobial peptide
LL-37
bactericidal peptide
Wound closure

Embargoed Document

White_etal_ACSID_A_Synthetic_Cyclized_AAM
Accepted author manuscript, 603 KB
Licence: Unspecified
Embargo ends: 19/04/24

Cite this

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title = "A synthetic cyclized antimicrobial peptide with potent effects against drug resistant skin pathogens",

abstract = "Dermal infections requiring treatment are usually treated with conventionalantibiotics, but the rise of bacterial resistance to first-line antibiotics warrants alternative therapeutics. Here, we report that a backbone-cyclized antimicrobial peptide, CD4-PP, designed from the human host defence peptide LL-37, has strong direct antibacterial effects on antibiotic sensitive as well as resistant type strains and clinical isolates of common skin pathogens in low (and treatment with CD4-PP is able to clear bacterial infections in infected keratinocytes.Additionally, CD4-PP treatment significantly reduces the wound area in a lawn ofkeratinocytes infected with MRSA. In conclusion, CD4-PP has the potential to serve as a future drug treating wounds infected with antibiotic resistant bacteria.",

keywords = "Keratinocytes;, MRSA, synthetic antimicrobial peptide, LL-37, bactericidal peptide, Wound closure",

author = "White, {John Kerr} and Soumitra Mohanty and Taj Muhammad and {de Arriba Sanchez de la Campa}, Magdalena and Houssen, {Wael E} and Natalia Ferraz and Ulf G{\"o}ransson and Annelie Brauner",

note = "Acknowledgments We would like to thank Anna Blasi-Romero for helping with the set-up of the initial scanning electron microscopy experiments. This project was partially supported by the Stiftelsen Olle Engkvist Byggm{\"a}stare (AB 186 678), Region Stockholm (AB, ALF project 995080), a fellowship grant from the EPSRC (no. EP/S027246/1, W.E.H.), the Bo Rydin Foundation (no. F30/20; NF), the Swedish Research Council (# no. 2011-3403; UG); and Postdoctoral scholarship by Elisabeth and Alfred Ahlqvists Stiftelse, Apotekarsocieteten (TM). The graphical abstract was created with a BioRender standard academic license.",

year = "2023",

month = apr,

day = "19",

language = "English",

journal = "ACS Infectious Diseases",

issn = "2373-8227",

publisher = "American Chemical Society",

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TY - JOUR

T1 - A synthetic cyclized antimicrobial peptide with potent effects against drug resistant skin pathogens

AU - White, John Kerr

AU - Mohanty, Soumitra

AU - Muhammad, Taj

AU - de Arriba Sanchez de la Campa, Magdalena

AU - Houssen, Wael E

AU - Ferraz, Natalia

AU - Göransson, Ulf

AU - Brauner, Annelie

N1 - Acknowledgments We would like to thank Anna Blasi-Romero for helping with the set-up of the initial scanning electron microscopy experiments. This project was partially supported by the Stiftelsen Olle Engkvist Byggmästare (AB 186 678), Region Stockholm (AB, ALF project 995080), a fellowship grant from the EPSRC (no. EP/S027246/1, W.E.H.), the Bo Rydin Foundation (no. F30/20; NF), the Swedish Research Council (# no. 2011-3403; UG); and Postdoctoral scholarship by Elisabeth and Alfred Ahlqvists Stiftelse, Apotekarsocieteten (TM). The graphical abstract was created with a BioRender standard academic license.

PY - 2023/4/19

Y1 - 2023/4/19

N2 - Dermal infections requiring treatment are usually treated with conventionalantibiotics, but the rise of bacterial resistance to first-line antibiotics warrants alternative therapeutics. Here, we report that a backbone-cyclized antimicrobial peptide, CD4-PP, designed from the human host defence peptide LL-37, has strong direct antibacterial effects on antibiotic sensitive as well as resistant type strains and clinical isolates of common skin pathogens in low (and treatment with CD4-PP is able to clear bacterial infections in infected keratinocytes.Additionally, CD4-PP treatment significantly reduces the wound area in a lawn ofkeratinocytes infected with MRSA. In conclusion, CD4-PP has the potential to serve as a future drug treating wounds infected with antibiotic resistant bacteria.

AB - Dermal infections requiring treatment are usually treated with conventionalantibiotics, but the rise of bacterial resistance to first-line antibiotics warrants alternative therapeutics. Here, we report that a backbone-cyclized antimicrobial peptide, CD4-PP, designed from the human host defence peptide LL-37, has strong direct antibacterial effects on antibiotic sensitive as well as resistant type strains and clinical isolates of common skin pathogens in low (and treatment with CD4-PP is able to clear bacterial infections in infected keratinocytes.Additionally, CD4-PP treatment significantly reduces the wound area in a lawn ofkeratinocytes infected with MRSA. In conclusion, CD4-PP has the potential to serve as a future drug treating wounds infected with antibiotic resistant bacteria.

KW - Keratinocytes;

KW - MRSA

KW - synthetic antimicrobial peptide

KW - LL-37

KW - bactericidal peptide

KW - Wound closure

M3 - Article

JO - ACS Infectious Diseases

JF - ACS Infectious Diseases

SN - 2373-8227

ER -

A synthetic cyclized antimicrobial peptide with potent effects against drug resistant skin pathogens

Abstract

Keywords

Embargoed Document

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