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

Brian C. O'Connell, Tao Xu, Thomas J. Walsh, Tin Sein, Andrea Mastrangeli, Ronald G. Crystal, Frank G. Oppenheim, Bruce J. Baum

Research output: Contribution to journalArticle

69 Citations (Scopus)

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 μg/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.

Original languageEnglish
Pages (from-to)2255-2261
Number of pages7
JournalHuman gene therapy
Volume7
Issue number18
DOIs
Publication statusPublished - 1 Dec 1996

    Fingerprint

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics

Cite this

O'Connell, B. C., Xu, T., Walsh, T. J., Sein, T., Mastrangeli, A., Crystal, R. G., Oppenheim, F. G., & Baum, B. J. (1996). Transfer of a gene encoding the anticandidal protein histatin 3 to salivary glands. Human gene therapy, 7(18), 2255-2261. https://doi.org/10.1089/hum.1996.7.18-2255