TY - JOUR
T1 - The antimicrobial peptide SAAP-148 combats drug-resistant bacteria and biofilms
AU - de Breij, Anna
AU - Riool, Martijn
AU - Cordfunke, Robert A.
AU - Malanovic, Nermina
AU - de Boer, Leonie
AU - Koning, Roman I.
AU - Ravensbergen, Elisabeth
AU - Franken, Marnix
AU - van der Heijde, Tobias
AU - Boekema, Bouke K.
AU - Kwakman, Paulus H. S.
AU - Kamp, Niels
AU - El Ghalbzouri, Abdelouahab
AU - Lohner, Karl
AU - Zaat, Sebastian A. J.
AU - Drijfhout, Jan W.
AU - Nibbering, Peter H.
PY - 2018
Y1 - 2018
N2 - 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
AB - 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
U2 - https://doi.org/10.1126/scitranslmed.aan4044
DO - https://doi.org/10.1126/scitranslmed.aan4044
M3 - Article
C2 - 29321257
SN - 1946-6242
VL - 10
SP - eaan4044
JO - Science Translational Medicine
JF - Science Translational Medicine
IS - 423
ER -