Transfer of a gene encoding the anticandidal protein histatin 3 to salivary glands.

Publication Type	Academic Article
Authors	O'Connell B, Xu T, Walsh T, Sein T, Mastrangeli A, Crystal R, Oppenheim F, Baum B
Journal	Hum Gene Ther
Volume	7
Issue	18
Pagination	2255-61
Date Published	12/01/1996
ISSN	1043-0342
Keywords	Candida albicans, Gene Transfer Techniques, Proteins, Salivary Glands, Salivary Proteins and Peptides
Abstract	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.
DOI	10.1089/hum.1996.7.18-2255
PubMed ID	8953316