Therapeutic targets for the treatment of microsporidiosis in humans

Abstract

Introduction: Microsporidia have been increasingly reported to infect humans. The most common presentation of microsporidia infection is chronic diarrhea which can be extremely debilitating and carries a significant mortality risk in immune compromised patients. Albendazole, which inhibits tubulin, and fumagillin, which inhibits methionine aminopeptidase type 2 (MetAP2), are currently the two main therapeutic agents used for microsporidiosis treatment. In addition, to their role as emerging pathogens in humans, the Microsporidia are important pathogens in commercially important 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 (TIM), Tubulin, Methionine aminopeptidase 2 (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 (MetAP1) and are, therefore, dependent on MetAP2, while mammalian cells have both enzymes. Thus, MetAP2 is an essential enzyme in the Microsporidia and new inhibitors of this pathway have significant promise as therapeutic agents.

Invasion of Host Cells by Microsporidia

“…Chitin is the main component of the endospore, and chitin has been reported to be the major component of fibrils that form bridges across the endospore and to be part of the fibrillary system of the exospores, which is essential in maintaining spore cell structure and function (Erickson and Blanquet, 1969;Han and Weiss, 2018). The presence of chitin in the spore wall is useful as a target of diagnosis as it can be stained by fluorescence dyes such as Calcofluor white or Uvitex 2B.…”

Occurrence, risk factors and genotypes of Enterocytozoon bieneusi in dogs and cats in Guangzhou, southern China: high genotype diversity and zoonotic concern

“…Not unexpectedly, deworming had a significantly negative effect on the risk of contracting E. bieneusi infections. But with no currently effective drugs against such infections [25], careful management of pet hygiene is very important.…”

Occurrence, risk factors and genotypes of Enterocytozoon bieneusi in dogs and cats in Guangzhou, southern China: high genotype diversity and zoonotic concern

“…Not unexpectedly, deworming had a signi cantly negative effect on the risk of contracting E. bieneusi infections. But with no currently effective drugs against such infections [25], careful management of pet hygiene is very important. Nevertheless, various factors like host immunity, climate, and geography may contribute to E. bieneusi infection rates, as does the sample size used in epidemiological studies on this fungi.…”