The antimicrobial peptide SAAP-148 combats drug-resistant bacteria and biofilms

  • Sci Transl Med. 2018 Jan 10;10(423):eaan4044. doi: 10.1126/scitranslmed.aan4044.
Anna de Breij  1 ,  Martijn Riool  2 ,  Robert A Cordfunke  3 ,  Nermina Malanovic  4 ,  Leonie de Boer  2 ,  Roman I Koning  5  6 ,  Elisabeth Ravensbergen  1 ,  Marnix Franken  1 ,  Tobias van der Heijde  1 ,  Bouke K Boekema  7 ,  Paulus H S Kwakman  2 ,  Niels Kamp  8 ,  Abdelouahab El Ghalbzouri  9 ,  Karl Lohner  4 ,  Sebastian A J Zaat  2 ,  Jan W Drijfhout  3 ,  Peter H Nibbering  10
Affiliations
  • 1. Department of Infectious Diseases, Leiden University Medical Center, 2300 RC Leiden, Netherlands.
  • 2. Department of Medical Microbiology, Amsterdam Infection and Immunity Institute, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, Netherlands.
  • 3. Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, 2300 RC Leiden, Netherlands.
  • 4. Biophysics Division, Institute of Molecular Biosciences, University of Graz, Naturwissenschaftliche Fakultät (NAWI) Graz, BioTechMed, 8010 Graz, Austria.
  • 5. Department of Molecular Cell Biology, Leiden University Medical Center, 2300 RC Leiden, Netherlands.
  • 6. Netherlands Center for Electron Nanoscopy, Institute of Biology Leiden, Leiden University, 2300 RA Leiden, Netherlands.
  • 7. Association of Dutch Burn Centres, 1942 LT Beverwijk, Netherlands.
  • 8. Animal Research Institute, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, Netherlands.
  • 9. Department of Dermatology, Leiden University Medical Center, 2300 RC Leiden, Netherlands.
  • 10. Department of Infectious Diseases, Leiden University Medical Center, 2300 RC Leiden, Netherlands. [email protected].
PMID: 29321257 DOI: 10.1126/scitranslmed.aan4044
Abstract

Development of novel antimicrobial agents is a top priority in the fight against multidrug-resistant (MDR) and persistent bacteria. We developed a panel of synthetic antimicrobial and antibiofilm peptides (SAAPs) with enhanced antimicrobial activities compared to the parent peptide, human antimicrobial peptide LL-37. Our lead peptide SAAP-148 was more efficient in killing bacteria under physiological conditions in vitro than many known preclinical- and clinical-phase antimicrobial peptides. SAAP-148 killed MDR pathogens without inducing resistance, prevented biofilm formation, and eliminated established biofilms and persister cells. A single 4-hour treatment with hypromellose ointment containing SAAP-148 completely eradicated acute and established, biofilm-associated infections with methicillin-resistant Staphylococcus aureus and MDR Acinetobacter baumannii from wounded ex vivo human skin and murine skin in vivo. Together, these data demonstrate that SAAP-148 is a promising drug candidate in the battle against antibiotic-resistant bacteria that pose a great threat to human health.

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