Analysis of the beta-tubulin gene and morphological changes of the microsporidium Anncaliia algerae both suggest albendazole sensitivity

J Eukaryot Microbiol. 2015 Jan-Feb;62(1):60-8. doi: 10.1111/jeu.12160. Epub 2014 Sep 15.

Abstract

The Microsporidium, Anncaliia algerae, an obligate intracellular parasite, has been identified as an opportunistic human pathogen, but treatment has not been evaluated for infections with this organism. Albendazole, an antitubulin polymerization drug used against parasitic worm infections, has been the medication of choice used to treat some microsporidial infections affecting humans, with varying results ranging from clearing infection (Encephalitozoon) to resistance (Enterocytozoon). This study illustrates the effect of albendazole treatment on A. algerae infection in Rabbit Kidney (RK13) cells and Human Fetal Lung (HFL-1) fibroblasts. Albendazole appears to have an attenuating effect on A. algerae infection and albendazole's IC50 in RK13 cells is 0.1 μg/ml. Long-term treatment inhibits up to 98% of spore production, but interrupting treatment reestablishes the infection without new exposure to the parasite as supported by microscopic observations. The parasite's beta-tubulin gene was purified, cloned, and sequenced. Five of the six specific amino acids, associated with benzimidazole sensitivity, are conserved in A. algerae. These findings suggest that A. algerae is sensitive to albendazole; however, the organism is not completely cleared from cultures.

Keywords: Benzimidazole effects; Microsporidia; drug treatment; electron microscopy; pathology.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Albendazole / pharmacology
  • Amino Acid Sequence
  • Animals
  • Benzimidazoles / pharmacology
  • Cell Line
  • Cloning, Molecular
  • Conserved Sequence
  • Epithelial Cells / drug effects
  • Epithelial Cells / microbiology
  • Fibroblasts / drug effects
  • Fibroblasts / microbiology
  • Fungal Proteins / genetics*
  • Fungal Proteins / metabolism
  • Gene Expression
  • Humans
  • Kidney
  • Lung
  • Microbial Sensitivity Tests
  • Microsporidia, Unclassified / drug effects*
  • Microsporidia, Unclassified / genetics
  • Microsporidia, Unclassified / metabolism
  • Microsporidia, Unclassified / ultrastructure
  • Molecular Sequence Data
  • Rabbits
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Sequence Alignment
  • Spores, Fungal / drug effects*
  • Spores, Fungal / genetics
  • Spores, Fungal / metabolism
  • Spores, Fungal / ultrastructure
  • Tubulin / genetics*
  • Tubulin / metabolism
  • Tubulin Modulators / pharmacology*

Substances

  • Benzimidazoles
  • Fungal Proteins
  • Recombinant Proteins
  • Tubulin
  • Tubulin Modulators
  • benzimidazole
  • Albendazole