Wakabayashi H, Abe S, Teraguchi S, Hayasawa H, Yamaguchi H
Nutritional Science Laboratory, Morinaga Milk Industry Co., Ltd., Kanagawa, Japan.
Antimicrob Agents Chemother. 1998 Jul;42(7):1587-91. doi: 10.1128/AAC.42.7.1587.
The effects of bovine lactoferrin (LF) or the LF-derived antimicrobial peptide lactoferricin B (LFcin B) on the growth of Candida albicans hyphae, including those of three azole-resistant strains, were investigated by a crystal violet staining method. The hyphae of two highly azole-resistant strains were more susceptible to inhibition by LF or LFcin B than the azole-susceptible strains tested. One moderately azole-resistant strain was defective in the formation of hyphae and showed a susceptibility to LF greater than that of the susceptible strains but a susceptibility to LFcin B similar to that of the susceptible strains. The highly azole-resistant strain TIMM3317 showed trailing growth in the presence of fluconazole or itraconazole, while the extent of growth was reduced by the addition of LF or LFcin B at a sub-MIC. Thus, the addition of LF or LFcin B at a sub-MIC resulted in a substantial decrease in the MICs of fluconazole and itraconazole for two highly azole-resistant strains; e.g., the MIC of fluconazole for TIMM3317 was shifted from > 256 to 0.25 micrograms/ml by LF, but the MICs were not decreased for the susceptible strains. The combination effects observed with triazoles and LF-related compounds in the case of the two highly azole-resistant strains were confirmed to be synergistic by the fractional inhibitory concentration index. These results demonstrate that for some azole-resistant C. albicans strains, LF-related compounds combined with triazoles can inhibit the growth of hyphae, an important form of this organism in pathogenesis.
采用结晶紫染色法,研究了牛乳铁蛋白(LF)或乳铁蛋白衍生的抗菌肽乳铁素B(LFcin B)对白色念珠菌菌丝生长的影响,其中包括三种耐唑类菌株。与所测试的唑类敏感菌株相比,两种高度耐唑类菌株的菌丝对LF或LFcin B的抑制作用更敏感。一种中度耐唑类菌株在菌丝形成方面存在缺陷,对LF的敏感性高于敏感菌株,但对LFcin B的敏感性与敏感菌株相似。高度耐唑类菌株TIMM3317在氟康唑或伊曲康唑存在下呈拖尾生长,而在亚抑菌浓度下添加LF或LFcin B可降低其生长程度。因此,在亚抑菌浓度下添加LF或LFcin B可使两种高度耐唑类菌株的氟康唑和伊曲康唑最低抑菌浓度(MIC)大幅降低;例如,LF使TIMM3317的氟康唑MIC从>256微克/毫升降至0.25微克/毫升,但敏感菌株的MIC并未降低。通过部分抑菌浓度指数证实,在两种高度耐唑类菌株中观察到的三唑类与LF相关化合物的联合作用具有协同性。这些结果表明,对于一些耐唑类白色念珠菌菌株,LF相关化合物与三唑类联合使用可抑制菌丝生长,而菌丝是该病原体在发病机制中的一种重要形态。