TY - JOUR

T1 - LL-37 fragments have antimicrobial activity against Staphylococcus epidermidis biofilms and wound healing potential in HaCaT cell line

AU - Saporito, Paola

AU - Vang Mouritzen, Michelle

AU - Løbner-Olesen, Anders

AU - Jenssen, Håvard

N1 - Copyright © 2018 European Peptide Society and John Wiley & Sons, Ltd.

PY - 2018

Y1 - 2018

N2 - Staphylococcus epidermidis is a common nosocomial pathogen able to form biofilms in indwelling devices, resulting in chronic infections, which are refractory to antibiotics treatment. Staphylococcal biofilms are also associated with the delayed reepithelization and healing of chronic wounds. The human cathelicidin peptide LL-37 has been proven active against S. epidermidis biofilms in vitro and to promote wound healing. As previous studies have demonstrated that fragments of LL-37 could possess an equal antibacterial activity as the parent peptide, we tested whether shorter (12-mer) synthetic fragments of LL-37 maintained the antibiofilm and/or immune modulating activity, aiming at the identification of essential regions within the LL-37 parent sequence. Three fragments of LL-37 displayed improved activity against S. epidermidis in terms of biofilm inhibition and eradication, a reduced cytotoxicity to human keratinocytes and erythrocytes. In addition, KR-12 and VQ-12V26 enhanced wound healing potential, relative to LL37. FK-12 and KR-12 are truncated version of the cathelicidin, previously reported as valid antimicrobials, whereas VQ-12V26 is a single substituted LL-37 fragment. Remarkably, the single substitution aspartic acid to valine in position 26 caused gain of antimicrobial function in the inactive VQ-12 fragment. The combination of antibiofilm, wound healing potential, and low cytotoxicity makes KR-12 and VQ-12V26 promising therapeutic agents and lead compounds for further improvement and understanding of antibiofilm and wound healing properties.

AB - Staphylococcus epidermidis is a common nosocomial pathogen able to form biofilms in indwelling devices, resulting in chronic infections, which are refractory to antibiotics treatment. Staphylococcal biofilms are also associated with the delayed reepithelization and healing of chronic wounds. The human cathelicidin peptide LL-37 has been proven active against S. epidermidis biofilms in vitro and to promote wound healing. As previous studies have demonstrated that fragments of LL-37 could possess an equal antibacterial activity as the parent peptide, we tested whether shorter (12-mer) synthetic fragments of LL-37 maintained the antibiofilm and/or immune modulating activity, aiming at the identification of essential regions within the LL-37 parent sequence. Three fragments of LL-37 displayed improved activity against S. epidermidis in terms of biofilm inhibition and eradication, a reduced cytotoxicity to human keratinocytes and erythrocytes. In addition, KR-12 and VQ-12V26 enhanced wound healing potential, relative to LL37. FK-12 and KR-12 are truncated version of the cathelicidin, previously reported as valid antimicrobials, whereas VQ-12V26 is a single substituted LL-37 fragment. Remarkably, the single substitution aspartic acid to valine in position 26 caused gain of antimicrobial function in the inactive VQ-12 fragment. The combination of antibiofilm, wound healing potential, and low cytotoxicity makes KR-12 and VQ-12V26 promising therapeutic agents and lead compounds for further improvement and understanding of antibiofilm and wound healing properties.

U2 - 10.1002/psc.3080

DO - 10.1002/psc.3080

M3 - Journal article

C2 - 29737589

VL - 24

JO - Journal of Peptide Science

JF - Journal of Peptide Science

SN - 1075-2617

IS - 7

M1 - e3080

T2 - IMAP 2017

Y2 - 25 August 2017 through 27 August 2017

ER -