Oral Ecology Research Group, Faculty of Dentistry, Laval University, 2420, rue de la Terrasse, Quebec G1V 0A6, QC, Canada.
BMC Microbiol. 2013 Nov 7;13:246. doi: 10.1186/1471-2180-13-246.
Antimicrobial peptides have been the focus of much research over the last decade because of their effectiveness and broad-spectrum activity against microbial pathogens. These peptides also participate in inflammation and the innate host defense system by modulating the immune function that promotes immune cell adhesion and migration as well as the respiratory burst, which makes them even more attractive as therapeutic agents. This has led to the synthesis of various antimicrobial peptides, including KSL-W (KKVVFWVKFK-NH2), for potential clinical use. Because this peptide displays antimicrobial activity against bacteria, we sought to determine its antifungal effect on C. albicans. Growth, hyphal form, biofilm formation, and degradation were thus examined along with EFG1, NRG1, EAP1, HWP1, and SAP 2-4-5-6 gene expression by quantitative RT-PCR.
This study demonstrates that KSL-W markedly reduced C. albicans growth at both early and late incubation times. The significant effect of KSL-W on C. albicans growth was observed beginning at 10 μg/ml after 5 h of contact by reducing C. albicans transition and at 25 μg/ml by completely inhibiting C. albicans transition. Cultured C. albicans under biofilm-inducing conditions revealed that both KSL-W and amphotericin B significantly decreased biofilm formation at 2, 4, and 6 days of culture. KSL-W also disrupted mature C. albicans biofilms. The effect of KSL-W on C. albicans growth, transition, and biofilm formation/disruption may thus occur through gene modulation, as the expression of various genes involved in C. albicans growth, transition and biofilm formation were all downregulated when C. albicans was treated with KSL-W. The effect was greater when C. albicans was cultured under hyphae-inducing conditions.
These data provide new insight into the efficacy of KSL-W against C. albicans and its potential use as an antifungal therapy.
在过去的十年中,由于其有效性和广谱活性对抗微生物病原体,抗菌肽一直是研究的焦点。这些肽还通过调节免疫功能参与炎症和先天宿主防御系统,促进免疫细胞的黏附和迁移以及呼吸爆发,这使得它们作为治疗剂更具吸引力。这导致了各种抗菌肽的合成,包括 KSL-W(KKVVFWVKFK-NH2),用于潜在的临床应用。由于这种肽对细菌显示出抗菌活性,我们试图确定其对白色念珠菌的抗真菌作用。因此,通过定量 RT-PCR 检查了生长、菌丝形成、生物膜形成和降解以及 EFG1、NRG1、EAP1、HWP1 和 SAP2-4-5-6 基因的表达。
这项研究表明,KSL-W 在早期和晚期孵育时间均显著降低白色念珠菌的生长。在接触后 5 小时,KSL-W 对白色念珠菌生长的显著影响开始显现,浓度为 10μg/ml 时,通过减少白色念珠菌的过渡,在 25μg/ml 时完全抑制白色念珠菌的过渡。在生物膜诱导条件下培养白色念珠菌,发现 KSL-W 和两性霉素 B 均能显著降低培养 2、4 和 6 天的生物膜形成。KSL-W 还破坏了成熟的白色念珠菌生物膜。KSL-W 对白色念珠菌生长、过渡和生物膜形成/破坏的影响可能是通过基因调节发生的,因为当白色念珠菌用 KSL-W 处理时,涉及白色念珠菌生长、过渡和生物膜形成的各种基因的表达均下调。在诱导菌丝形成的条件下培养白色念珠菌时,效果更大。
这些数据为 KSL-W 对抗白色念珠菌的功效及其作为抗真菌治疗的潜在用途提供了新的见解。