Transfer of a gene encoding the anticandidal protein histatin 3 to salivary glands. Academic Article uri icon

Overview

MeSH

  • Adenoviridae
  • Animals
  • Antifungal Agents
  • Cell Line
  • DNA, Recombinant
  • Epithelial Cells
  • Fluconazole
  • Gene Expression
  • Genetic Vectors
  • Histatins
  • Humans
  • Male
  • Microbial Sensitivity Tests
  • RNA, Messenger
  • Rats
  • Rats, Wistar
  • Recombinant Proteins
  • Saliva
  • Submandibular Gland

MeSH Major

  • 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.

publication date

  • December 1, 1996

has subject area

  • Adenoviridae
  • Animals
  • Antifungal Agents
  • Candida albicans
  • Cell Line
  • DNA, Recombinant
  • Epithelial Cells
  • Fluconazole
  • Gene Expression
  • Gene Transfer Techniques
  • Genetic Vectors
  • Histatins
  • Humans
  • Male
  • Microbial Sensitivity Tests
  • Proteins
  • RNA, Messenger
  • Rats
  • Rats, Wistar
  • Recombinant Proteins
  • Saliva
  • Salivary Glands
  • Salivary Proteins and Peptides
  • Submandibular Gland

Research

keywords

  • Journal Article

Identity

Language

  • eng

Digital Object Identifier (DOI)

  • 10.1089/hum.1996.7.18-2255

PubMed ID

  • 8953316

Additional Document Info

start page

  • 2255

end page

  • 2261

volume

  • 7

number

  • 18