Candida albicans is a commensal organism and opportunistic pathogen that can form biofilms that colonize surfaces of medical devices, such as implants, catheters, and dentures. Compared to planktonic C. albicans cells, cells in biofilms exhibit increased resistance to treatment. Histatin 5 (Hst-5) is an antimicrobial peptide that is natively secreted by human salivary glands and has strong antifungal activity against C. albicans. However, C. albicans produces secreted aspartic proteases (Saps) that can cleave and inactivate Hst-5, limiting its antifungal properties. We previously showed that residue substitutions K11R and K17R within Hst-5 improve its antifungal activity and prevent proteolytic degradation by Saps when treating planktonic C. albicans. Here, we investigated the use of the K11R-K17R peptide as an alternative therapeutic against C. albicans biofilms by assessing its ability to reduce viability of pre-formed biofilms and to inhibit the formation of biofilms and showed that K11R-K17R had improved activity compared to Hst-5. Based on these results, we incorporated K11R-K17R and Hst-5 into polyelectrolyte multilayer (PEM) surface coatings and demonstrated that films functionalized with K11R-K17R reduced the formation of C. albicans biofilms. Our results demonstrate the therapeutic potential of the K11R-K17R Hst-5 variant in preventing and treating biofilms.

白色念珠菌是一种共生生物和机会性病原体，可形成生物膜，在医疗器械（如植入物、导管和假牙）表面定植。与浮游的白色念珠菌细胞相比，生物膜中的细胞表现出对治疗的抵抗力增加。组氨酸 5 (Hst-5) 是一种由人类唾液腺天然分泌的抗菌肽，对白色念珠菌具有很强的抗真菌活性。然而，白色念珠菌会产生分泌的天冬氨酸蛋白酶 (SAP)，它可以切割和灭活 Hst-5，从而限制其抗真菌特性。我们之前表明，Hst-5 中的残基取代 K11R 和 K17R 可提高其抗真菌活性并防止树液在处理浮游生物时进行蛋白水解降解白色念珠菌。在这里，我们通过评估 K11R-K17R 肽降低预先形成的生物膜的活力和抑制生物膜形成的能力，研究了 K11R-K17R 肽作为针对白色念珠菌生物膜的替代治疗剂的用途，并表明 K11R-K17R 相比具有改善的活性到 Hst-5。基于这些结果，我们将 K11R-K17R 和 Hst-5 加入聚电解质多层 (PEM) 表面涂层中，并证明用 K11R-K17R 功能化的薄膜减少了白色念珠菌生物膜的形成。我们的结果证明了 K11R-K17R Hst-5 变体在预防和治疗生物膜方面的治疗潜力。