In vitro synergic antifungal effect of MUC7 12-mer with histatin-5 12-mer or miconazole
In vitro synergic antifungal effect of MUC7 12-mer with histatin-5 12-mer or miconazole
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DOI：
10.1093/jac/dkh181
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发表时间：
2004-05-01
影响因子：
5.2
通讯作者：
Bobek, LA
中科院分区：
文献类型：
--
作者：
Wei, GX;Bobek, LA
目的：MUC 7 12-mer（RKSYKCLHKRCR）是一种来源于人唾液MUC 7粘蛋白的阳离子肽，通过磷酸盐缓冲液中的杀伤试验测定，显示出有效的体外抗真菌活性。方法：采用微量肉汤稀释法测定MUC 7 12-mer和其他化合物对多种真菌的最低抑菌浓度（MIC）和最低杀菌浓度（MFC），并与其他化合物联合应用，测定MUC 7 12-mer和其他化合物对多种真菌的抑菌活性。还通过杀伤测定和肽介导的杀伤的时间动力学来确定白色念珠菌和新型隐球菌的活力。MUC 7 12-mer与其它化合物[组蛋白-5（Hsn 5）12-mer：AKRHHGYKRKFH、阿替西霉素B或咪康唑]组合对C.白色念珠菌和C.通过棋盘测定法确定新形式癌，并通过杀伤测定法确认。结果：MUC 7 12-mer的MIC和MFC在3.13 ~ 6.25 mg/L之间，与红霉素B和咪康唑（0.78-6.25 mg/L）相当。MUC 7 12-mer和Hsn 5 12-mer的ED 50值分别为7.1和7.4 μ M（或11.2和11.6 mg/L）。白色念珠菌分别为1.2和1.1 μ M（或1.9和1.7 mg/L）。新人类杀死C。白色念珠菌和C.分别在暴露于所述肽30和10分钟后获得新生动物。MUC 7 12-mer与Hsn 5 12-mer、MUC 7 12-mer与咪康唑联合应用对C.对新生隐球菌的部分抑制浓度指数（FICI）分别为0.37和0.25，对新生隐球菌的作用略低于协同作用。白色念珠菌，FICI分别为0.63和0.56。此外，使用人红细胞，两个唾液肽表现出低水平的溶血activity.Conclusions：这项研究表明，MUC 7 12-mer和Hsn 5 12-mer肽可能是合适的候选人，用于组合抗真菌治疗。
Objectives: MUC7 12-mer (RKSYKCLHKRCR), a cationic peptide derived from human salivary MUC7 mucin, exhibits potent in vitro antifungal activity, as determined by killing assays in phosphate buffer. In this study we examined the MUC7 12-mer antifungal activity alone or in combination with other antifungal agents in LYM medium (modified RPMI 1640).Methods: Antifungal activities of MUC7 12-mer and other compounds against several fungal strains were first measured by MIC and minimum fungicidal concentration (MFC) tests using broth microdilution assay. The viability of Candida albicans and Cryptococcus neoformans were also determined by killing assays and time kinetics of peptide-mediated killing. Antifungal activities of MUC7 12-mer in combination with other compounds [histatin-5 (Hsn5) 12-mer: AKRHHGYKRKFH, amphotericin B or miconazole] against C. albicans and C. neoformans were determined by chequerboard assays and confirmed by killing assays. Toxicities of individual compounds were determined by haemolytic assays.Results: MICs and MFCs of MUC7 12-mer ranged from 3.13 to 6.25 mg/L for most of the strains tested, and were, in most cases, comparable to those of amphotericin B and miconazole (0.78-6.25 mg/L). ED50 values of MUC7 12-mer and Hsn5 12-mer were 7.1 and 7.4 muM (or 11.2 and 11.6 mg/L), respectively, for C. albicans; and 1.2 and 1.1 muM (or 1.9 and 1.7 mg/L), respectively, for C. neoformans. The killing of C. albicans and C. neoformans was achieved after 30 and 10 min exposure to the peptides, respectively. Combinations of MUC7 12-mer and Hsn5 12-mer, and of MUC7 12-mer and miconazole have a synergic antifungal effect on C. neoformans, with a fractional inhibitory concentration index (FICI) of 0.37 and 0.25, respectively; and a slightly lower than synergic effect on C. albicans, with a FICI of 0.63 and 0.56, respectively. In addition, using human erythrocytes, the two salivary peptides showed low levels of haemolytic activity.Conclusions: This study suggests that MUC7 12-mer and Hsn5 12-mer peptides may be suitable candidates for use in combination antifungal therapy.