Therapeutic targets for the treatment of microsporidiosis in humans

Expert Opin Ther Targets. 2018 Nov;22(11):903-915. doi: 10.1080/14728222.2018.1538360. Epub 2018 Nov 1.

Abstract

Microsporidia have been increasingly reported to infect humans. The most common presentation of microsporidiosis is chronic diarrhea, a significant mortality risk in immune-compromised patients. Albendazole, which inhibits tubulin, and fumagillin, which inhibits methionine aminopeptidase type 2 (MetAP2), are the two main therapeutic agents used for treatment of microsporidiosis. In addition, to their role as emerging pathogens in humans, microsporidia are important pathogens in insects, aquaculture, and veterinary medicine. New therapeutic targets and therapies have become a recent focus of attention for medicine, veterinary, and agricultural use. Areas covered: Herein, we discuss the detection and symptoms of microsporidiosis in humans and the therapeutic targets that have been utilized for the design of new drugs for the treatment of this infection, including triosephosphate isomerase, tubulin, MetAP2, topoisomerase IV, chitin synthases, and polyamines. Expert opinion: Enterocytozoon bieneusi is the most common microsporidia in human infection. Fumagillin has a broader anti-microsporidian activity than albendazole and is active against both Ent. bieneusi and Encephaliozoonidae. Microsporidia lack methionine aminopeptidase type 1 and are, therefore, dependent on MetAP2, while mammalian cells have both enzymes. Thus, MetAP2 is an essential enzyme in microsporidia and new inhibitors of this pathway have significant promise as therapeutic agents.

Keywords: Chitin synthases; Microsporidia; diagnosis; methionine aminopeptidase 2; microsporidiosis; polyamines; therapeutic targets; triosephosphate isomerase; tubulin.

Publication types

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

MeSH terms

  • Albendazole / pharmacology
  • Animals
  • Antifungal Agents / pharmacology*
  • Cyclohexanes / pharmacology
  • Drug Design
  • Fatty Acids, Unsaturated / pharmacology
  • Humans
  • Microsporidia / drug effects
  • Microsporidia / isolation & purification
  • Microsporidiosis / drug therapy*
  • Microsporidiosis / microbiology
  • Molecular Targeted Therapy*
  • Sesquiterpenes / pharmacology

Substances

  • Antifungal Agents
  • Cyclohexanes
  • Fatty Acids, Unsaturated
  • Sesquiterpenes
  • fumagillin
  • Albendazole