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de Breij, Anna; Riool, Martijn; Cordfunke, Robert A; Malanovic, Nermina; de Boer, Leonie; Koning, Roman I; Ravensbergen, Elisabeth; Franken, Marnix; van der Heijde, Tobias; Boekema, Bouke K; Kwakman, Paulus H S; Kamp, Niels; El Ghalbzouri, Abdelouahab; Lohner, Karl; Zaat, Sebastian A J; Drijfhout, Jan W; Nibbering, Peter H
Science translational medicine, 01/2018, Letnik: 10, Številka: 423Journal Article
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 and MDR 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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in: SICRIS
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