López-García Belén, Lee Phillip H A, Yamasaki Kenshi, Gallo Richard L
Division of Dermatology, University of California San Diego, and VA San Diego Healthcare Center, San Diego, California 92161, USA.
J Invest Dermatol. 2005 Jul;125(1):108-15. doi: 10.1111/j.0022-202X.2005.23713.x.
Cathelicidins have broad anti-microbial capacity and are important for host defense against skin infections by some bacterial and viral pathogens. This study investigated the activity of cathelicidins against Candida albicans. The human cathelicidin LL-37, and mouse cathelicidin mCRAMP, killed C. albicans, but this fungicidal activity was dependent on culture conditions. Evaluation of the fungal membrane by fluorescent dye penetration after incubation with cathelicidins correlated membrane permeabilization and inhibition of fungal growth. Anti-fungal assays carried out in an ionic environment that mimicked human sweat and with the processed forms of cathelicidin such as are present in sweat found that the cleavage of LL-37 to forms such as RK-31 conferred additional activity against C. albicans. C. albicans also induced an increase in the expression of cathelicidin in mouse skin, but this induction did not confer systemic or subcutaneous resistance as mCRAMP-deficient mice were not more susceptible to C. albicans in blood-killing assays or in an intradermal infection model. Therefore, cathelicidins appear active against C. albicans, but may be most effective as a superficial barrier to infection.
抗菌肽具有广泛的抗菌能力,对于宿主抵御某些细菌和病毒病原体引起的皮肤感染至关重要。本研究调查了抗菌肽对白色念珠菌的活性。人抗菌肽LL-37和小鼠抗菌肽mCRAMP可杀死白色念珠菌,但这种杀菌活性取决于培养条件。用抗菌肽孵育后通过荧光染料渗透评估真菌细胞膜,结果表明膜通透性与真菌生长抑制相关。在模拟人类汗液的离子环境中以及使用汗液中存在的抗菌肽加工形式进行的抗真菌试验发现,LL-37裂解为RK-31等形式可赋予对白色念珠菌的额外活性。白色念珠菌还可诱导小鼠皮肤中抗菌肽表达增加,但这种诱导并未产生全身性或皮下抗性,因为在血液杀伤试验或皮内感染模型中,缺乏mCRAMP的小鼠对白色念珠菌并不更易感。因此,抗菌肽似乎对白色念珠菌有活性,但可能作为感染的表面屏障最为有效。