LL-37-derived peptides eradicate multidrug-resistant Staphylococcus aureus from thermally wounded human skin equivalents.
Burn wound infections are often difficult to treat due to the presence of multidrug-resistant bacterial strains and biofilms. Currently, mupirocin is used to eradicate methicillin-resistant Staphylococcus aureus (MRSA) from colonized persons; however, mupirocin resistance is also emerging. Since we consider antimicrobial peptides to be promising candidates for the development of novel anti-infective agents, we studied the antibacterial activities of a set of synthetic peptides against different strains of S. aureus, including mupirocin-resistant MRSA strains. The peptides were derived from P60.4Ac, a peptide based on the human cathelicidin LL-37. The results showed that peptide 10 (P10) was the only peptide more efficient than P60.4Ac, which is better than LL-37, in killing MRSA strain LUH14616. All three peptides displayed good antibiofilm activities. However, both P10 and P60.4Ac were more efficient than LL-37 in eliminating biofilm-associated bacteria. No toxic effects of these three peptides on human epidermal models were detected, as observed morphologically and by staining for mitochondrial activity. In addition, P60.4Ac and P10, but not LL-37, eradicated MRSA LUH14616 and the mupirocin-resistant MRSA strain LUH15051 from thermally wounded human skin equivalents (HSE). Interestingly, P60.4Ac and P10, but not mupirocin, eradicated LUH15051 from the HSEs. None of the peptides affected the excretion of interleukin 8 (IL-8) by thermally wounded HSEs upon MRSA exposure. In conclusion, the synthetic peptides P60.4Ac and P10 appear to be attractive candidates for the development of novel local therapies to treat patients with burn wounds infected with multidrug-resistant bacteria.
Department of Infectious Diseases, Leiden University Medical Center, Leiden, The Netherlands Department of Dermatology, Leiden University Medical Center, Leiden, The Netherlands e.m.haisma@lumc.nl.
Elisabeth M
EM
Haisma
Department of Infectious Diseases, Leiden University Medical Center, Leiden, The Netherlands.
Anna
A
de Breij
Department of Infectious Diseases, Leiden University Medical Center, Leiden, The Netherlands.
Heelam
H
Chan
Department of Infectious Diseases, Leiden University Medical Center, Leiden, The Netherlands.
Jaap T
JT
van Dissel
Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands.
Jan W
JW
Drijfhout
Department of Pulmonology, Leiden University Medical Center, Leiden, The Netherlands.
Pieter S
PS
Hiemstra
Department of Dermatology, Leiden University Medical Center, Leiden, The Netherlands.
Abdoelwaheb
A
El Ghalbzouri
Department of Infectious Diseases, Leiden University Medical Center, Leiden, The Netherlands.
Peter H
PH
Nibbering
D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D023181:Antimicrobial Cationic Peptides / Q000138:chemical synthesis / Q000494:pharmacology*; D018441:Biofilms / Q000187:drug effects* / Q000254:growth & development; D002058:Burns, Electric / Q000188:drug therapy* / Q000382:microbiology; D004817:Epidermis / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D006801:Humans; D016209:Interleukin-8 / Q000096:biosynthesis / Q000378:metabolism; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects / Q000254:growth & development; D008826:Microbial Sensitivity Tests; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008954:Models, Biological; D008969:Molecular Sequence Data; D016712:Mupirocin / Q000494:pharmacology; D017768:Skin, Artificial / Q000382:microbiology*; D060327:Solid-Phase Synthesis Techniques; D014947:Wounds and Injuries / Q000188:drug therapy* / Q000382:microbiology; D054804:Cathelicidins
D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; D016209:Interleukin-8; D016712:Mupirocin; D054804:Cathelicidins