The antimicrobial peptide SAAP-148 combats drug-resistant bacteria and biofilms
The antimicrobial peptide SAAP-148 combats drug-resistant bacteria and biofilms
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DOI：
10.1126/scitranslmed.aan4044
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发表时间：
2018-01-10
影响因子：
17.1
通讯作者：
Nibbering, Peter H.
中科院分区：
文献类型：
--
作者：
de Breij, Anna;Riool, Martijn;Nibbering, Peter H.
开发新型抗菌剂是对抗多药耐药(MDR)和持久性细菌的首要任务。我们开发了一组合成的抗菌肽(SAAP)，与母肽-人抗菌肽LL-37相比，SAAP的抗菌活性增强。我们的先导肽SAAP-148在体外生理条件下比许多已知的临床前和临床阶段的抗菌肽更有效地杀灭细菌。SAAP-148在不诱导耐药性的情况下杀灭多药耐药病原体，防止生物膜的形成，并消除已形成的生物膜和伴随体细胞。使用含有SAAP-148的海普乐软膏进行4小时的单一治疗，即可完全根除体内受伤的人和小鼠皮肤上的耐甲氧西林金黄色葡萄球菌和多药耐药鲍曼不动杆菌的急性和已建立的生物被膜相关感染。综上所述，这些数据表明，SAAP-148在对抗对人类健康构成巨大威胁的抗生素耐药细菌的战斗中是一种有前途的候选药物。
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.