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 |