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 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
Externally publishedYes

Fingerprint

Histatins
Salivary Glands
Candidiasis
Saliva
Fluconazole
Genes
Proteins
Candida albicans
Adenoviridae
HIV
Azoles
Mycoses
Opportunistic Infections
Germination
Acquired Immunodeficiency Syndrome
Complementary DNA
Morbidity
Infection

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., ... 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

Transfer of a gene encoding the anticandidal protein histatin 3 to salivary glands. / O'Connell, Brian C.; Xu, Tao; Walsh, Thomas J.; Sein, Tin; Mastrangeli, Andrea; Crystal, Ronald; Oppenheim, Frank G.; Baum, Bruce J.

In: Human Gene Therapy, Vol. 7, No. 18, 01.12.1996, p. 2255-2261.

Research output: Contribution to journalArticle

O'Connell, BC, Xu, T, Walsh, TJ, Sein, T, Mastrangeli, A, Crystal, R, Oppenheim, FG & Baum, BJ 1996, 'Transfer of a gene encoding the anticandidal protein histatin 3 to salivary glands', Human Gene Therapy, vol. 7, no. 18, pp. 2255-2261. https://doi.org/10.1089/hum.1996.7.18-2255
O'Connell, Brian C. ; Xu, Tao ; Walsh, Thomas J. ; Sein, Tin ; Mastrangeli, Andrea ; Crystal, Ronald ; Oppenheim, Frank G. ; Baum, Bruce J. / Transfer of a gene encoding the anticandidal protein histatin 3 to salivary glands. In: Human Gene Therapy. 1996 ; Vol. 7, No. 18. pp. 2255-2261.
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