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.

在抗多药耐药性（MDR）和持久性细菌的斗争中，开发新型抗菌剂是当务之急。我们开发了一组合成的抗微生物和抗生物膜肽（SAAP），与母体肽人抗微生物肽LL-37相比，具有增强的抗微生物活性。我们的先导肽SAAP-148在体外在生理条件下杀死细菌的能力比许多已知的临床前和临床阶段的抗菌肽更有效。SAAP-148可以杀死MDR病原体而不会产生耐药性，可以防止生物膜形成，并且可以消除已建立的生物膜和持久性细胞。用含有SAAP-148的羟丙甲纤维素软膏进行的单次4小时治疗可完全消除对甲氧西林耐药的急性和已确立的生物膜相关感染来自受伤的离体人皮肤和体内鼠皮肤的金黄色葡萄球菌和MDR鲍曼不动杆菌。总之，这些数据表明，SAAP-148在对抗对人类健康构成巨大威胁的抗药性细菌的斗争中是有前途的候选药物。