Research ArticleANTIMICROBIALS

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

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Science Translational Medicine  10 Jan 2018:
Vol. 10, Issue 423, eaan4044
DOI: 10.1126/scitranslmed.aan4044

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New way to keep bacteria at bay

Antibiotic resistance is a major threat to public health. To develop a new type of weapon in the arms race against bacteria, de Breij et al. generated a panel of synthetic peptides based on the human antimicrobial peptide LL-37. The lead candidate from this panel, SAAP-148, can kill dangerous antibiotic-resistant pathogens in many contexts, including on ex vivo human skin and in biofilms. Long-term exposure to SAAP-148 did not induce bacterial resistance. Topical application of SAAP-148 could one day be used in hospitals to help patients combat bacteria resistant to traditional antibiotics.

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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