O'Connell B C, Xu T, Walsh T J, Sein T, Mastrangeli A, Crystal R G, Oppenheim F G, Baum B J
Clinical Investigations and Patient Care Branch, National Institute of Dental Research, National Institutes of Health, Bethesda, MD 20892, USA.
Hum Gene Ther. 1996 Dec 1;7(18):2255-61. doi: 10.1089/hum.1996.7.18-2255.
Mucosal candidiasis, the most common opportunistic fungal infection in human immunodeficiency virus (HIV)-infected patients, is an early sign of clinically overt acquired immunodeficiency syndrome (AIDS) and an important cause of morbidity, particularly in HIV-infected children. The appearance of azole-resistant strains of Candida albicans had made clinical management of candidiasis increasingly difficult. We propose a novel approach to the management of candidal infections that involves the use of naturally occurring antifungal proteins, such as the histatins. Histatins are a family of small proteins that are secreted in human saliva. We have constructed recombinant adenovirus vectors that contain the histatin 3 cDNA. These vectors are capable of directing the expression of histatin 3 in the saliva of rats at up to 1,045 micrograms/ml, well above the levels found in normal human saliva. The adenovirus-directed histatin demonstrated a 90% candidacidal effect in the timed-kill assay against both fluconazole-susceptible and fluconazole-resistant strains of C. albicans and inhibited germination by 45% in the same strains. These studies suggest that a gene transfer approach to overexpress naturally occurring antifungal proteins may be useful in the management of mucosal candidiasis.
黏膜念珠菌病是人类免疫缺陷病毒（HIV）感染患者中最常见的机会性真菌感染，是临床明显的获得性免疫缺陷综合征（AIDS）的早期迹象，也是发病的重要原因，尤其是在HIV感染儿童中。白色念珠菌唑类耐药菌株的出现使念珠菌病的临床管理日益困难。我们提出了一种治疗念珠菌感染的新方法，该方法涉及使用天然存在的抗真菌蛋白，如组蛋白。组蛋白是在人类唾液中分泌的一类小蛋白。我们构建了包含组蛋白3 cDNA的重组腺病毒载体。这些载体能够在大鼠唾液中指导组蛋白3的表达，表达量高达1045微克/毫升，远高于正常人唾液中的水平。腺病毒介导的组蛋白在对白色念珠菌的氟康唑敏感和氟康唑耐药菌株的定时杀菌试验中显示出90%的杀念珠菌效果，并且在相同菌株中抑制发芽45%。这些研究表明，通过基因转移方法过表达天然存在的抗真菌蛋白可能对黏膜念珠菌病的治疗有用。
