Riptide Bioscience, Inc., Vallejo, California, USA
Riptide Bioscience, Inc., Vallejo, California, USA.
Antimicrob Agents Chemother. 2019 Oct 22;63(11). doi: 10.1128/AAC.02690-18. Print 2019 Nov.
Recurrent vulvovaginal candidiasis (RVVC) is a widespread chronic infection that has a substantial negative impact on work and quality of life. The development of antimicrobial resistance and biofilm formation are speculated to contribute to pathogenicity and treatment ineffectiveness. Designed antimicrobial peptides (dAMPs) are chemically modified from endogenous antimicrobial peptides that provide the first line of defense against pathogens. The goal here is to identify a dAMP for the topical treatment of RVVC. The dAMP MICs were determined for 46 fluconazole-susceptible and fluconazole-resistant spp. clinical isolates. The possibility of inducing dAMP drug resistance and comparison of dAMP and fluconazole activity against preformed biofilm and biofilm formation were evaluated. Assessment of mammalian cell viability was determined using bioluminescent human keratinocytes. The dAMP effect on fungus was probed via scanning electron microscopy, and topically applied dAMP activity was evaluated in a rodent vulvovaginal candidiasis (VVC) infection model. dAMPs demonstrated broad-spectrum antimicrobial activity against common causative clinical isolates, reduced preformed biofilm, and inhibited biofilm formation. An evaluated dAMP did not induce resistance after repeated exposure of The dAMPs were selective for cells with limited mammalian cytotoxicity with substantial activity in a rodent VVC model. dAMPs are described as having potent antifungal and antibiofilm activity, likely direct membrane action with selectivity for cells, with limited resistance development. Combined with activity in a rodent VVC model, the data support clinical evaluation of dAMPs for topical treatment of VCC and recurrent VVC infections.
复发性外阴阴道念珠菌病 (RVVC) 是一种广泛存在的慢性感染，对工作和生活质量有很大的负面影响。抗菌药物耐药性的发展和生物膜的形成被认为是导致致病性和治疗无效的原因。设计抗菌肽 (dAMP) 是从内源性抗菌肽化学修饰而来的，是抵御病原体的第一道防线。目的是确定一种用于 RVVC 局部治疗的 dAMP。测定了 46 株氟康唑敏感和氟康唑耐药 的 dAMP MICs 临床分离株。评估了诱导 dAMP 耐药的可能性，并比较了 dAMP 和氟康唑对预先形成的 生物膜和生物膜形成的活性。通过生物发光人角质形成细胞评估哺乳动物细胞活力。通过扫描电子显微镜探测 dAMP 对真菌的作用，并在啮齿动物外阴阴道念珠菌病 (VVC) 感染模型中评估局部应用 dAMP 的活性。dAMP 对常见致病临床 分离株具有广谱抗菌活性，减少了预先形成的生物膜，并抑制了生物膜的形成。经反复暴露后，评价的 dAMP 未诱导耐药。dAMP 对 细胞具有选择性，对哺乳动物的细胞毒性有限，在啮齿动物 VVC 模型中具有显著活性。dAMP 具有很强的抗真菌和抗生物膜活性，可能通过直接作用于细胞膜，对 细胞具有选择性，耐药性发展有限。结合在啮齿动物 VVC 模型中的活性，数据支持临床评估 dAMP 用于治疗 VCC 和复发性 VVC 感染的局部治疗。
