The novel antimicrobial peptide PXL150 in the local treatment of skin and soft tissue infections.
Dramatic increase in bacterial resistance towards conventional antibiotics emphasises the importance to identify novel, more potent antimicrobial therapies. Antimicrobial peptides (AMPs) have emerged as a promising new group to be evaluated in therapeutic intervention of infectious diseases. Here we describe a novel AMP, PXL150, which demonstrates in vitro a broad spectrum microbicidal action against both Gram-positive and Gram-negative bacteria, including resistant strains. The potent microbicidal activity and broad antibacterial spectrum of PXL150 were not associated with any hemolytic activity. Staphylococcus aureus and methicillin-resistant S. aureus (MRSA) failed to develop resistance towards PXL150 during continued selection pressure. PXL150 caused a rapid depolarisation of cytoplasmic membrane of S. aureus, and dissipating membrane potential is likely one mechanism for PXL150 to kill its target bacteria. Studies in human cell lines indicated that PXL150 has anti-inflammatory properties, which might be of additional benefit. PXL150 demonstrated pronounced anti-infectious effect in an in vivo model of full thickness wounds infected with MRSA in rats and in an ex vivo model of pig skin infected with S. aureus. Subcutaneous or topical application of the peptide in rats did not lead to any adverse reactions. In conclusion, PXL150 may constitute a new therapeutic alternative for local treatment of infections, and further studies are warranted to evaluate the applicability of this AMP in clinical settings.
Pergamum AB, Arvid Wallgrens Backe 20, 413 46, Gothenburg, Sweden.
Emma
E
Myhrman
Joakim
J
Håkansson
Kerstin
K
Lindgren
Camilla
C
Björn
Veronika
V
Sjöstrand
Margit
M
Mahlapuu
D000287:Administration, Topical; D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology / Q000633:toxicity; D002460:Cell Line; D002462:Cell Membrane / Q000187:drug effects; D004195:Disease Models, Animal; D004912:Erythrocytes; D006090:Gram-Negative Bacteria / Q000187:drug effects; D006094:Gram-Positive Bacteria / Q000187:drug effects; D006461:Hemolysis; D006801:Humans; D008826:Microbial Sensitivity Tests; D050296:Microbial Viability / Q000187:drug effects; D051381:Rats; D018461:Soft Tissue Infections / Q000188:drug therapy* / Q000382:microbiology; D013203:Staphylococcal Infections / Q000188:drug therapy* / Q000382:microbiology; D013207:Staphylococcal Skin Infections / Q000188:drug therapy* / Q000382:microbiology; D013552:Swine; D014946:Wound Infection / Q000188:drug therapy* / Q000382:microbiology
D023181:Antimicrobial Cationic Peptides