Investigations into microsporidian methionine aminopeptidase type 2: A therapeutic target for microsporidiosis

Hong Zhang, Huan Huang, Ann Cali, Peter M. Takvorian, Xiaochuan Feng, Ghou Zhou, Louis M. Weiss

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

The Microsporidia have been reported to cause a wide range of clinical diseases particularly in patients that are immunosuppressed. They can infect virtually any organ system and cases of gastrointestinal infection, encephalitis, ocular infection, sinusitis, myositis and disseminated infection are well described in the literature. While benzimidazoles such as albendazole are active against many species of Microsporidia, these drugs do not have significant activity against Enterocytozoon bieneusi. Fumagillin, ovalicin and their analogues have been demonstrated to have antimicrosporidial activity in vitro and in animal models of microsporidiosis. Fumagillin has also been demonstrated to have efficacy in human infections due to E. bieneusi. Fumagillin is an irreversible inhibitor of methionine aminopeptidase type 2 (MetAP2). Homology cloning employing the polymerase chain reaction was used to identify the MetAP2 gene from the human pathogenic microsporidia Encephalitozoon cuniculi, Encephalitozoon hellem, Encephalitozoon intestinalis, Brachiola algerae and E. bieneusi. The full-length MetAP2 coding sequence was obtained for all of the Encephalitozoonidae. Recombinant E. cuniculi MetAP2 was produced in baculovirus and purified using chromatographic techniques. The in vitro activity and effect of the inhibitors bestatin and TNP-470 on this recombinant microsporidian MetAP2 was characterized. An in silico model of E. cuniculi MetAP2 was developed based on crystallographic data on human MetAP2. These reagents provide new tools for the development of in vitro assay systems to screen candidate compounds for use as new therapeutic agents for the treatment of microsporidiosis.

Original languageEnglish (US)
Pages (from-to)182-192
Number of pages11
JournalFolia Parasitologica
Volume52
Issue number1-2
StatePublished - May 2005

Fingerprint

Microsporidiosis
microsporidiosis
aminopeptidases
Microsporidia
methionine
Enterocytozoon
Encephalitozoon cuniculi
therapeutics
Encephalitozoon
infection
Therapeutics
Encephalitozoon hellem
Benzimidazoles
benzimidazoles
sinusitis
myositis
Eye Infections
Albendazole
albendazole
Myositis

Keywords

  • Brachiola
  • Encephalitozoon
  • Enterocytozoon
  • MetAP2
  • Methionine aminopeptidase type 2
  • Microsporidia
  • Therapeutics

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Parasitology

Cite this

Investigations into microsporidian methionine aminopeptidase type 2 : A therapeutic target for microsporidiosis. / Zhang, Hong; Huang, Huan; Cali, Ann; Takvorian, Peter M.; Feng, Xiaochuan; Zhou, Ghou; Weiss, Louis M.

In: Folia Parasitologica, Vol. 52, No. 1-2, 05.2005, p. 182-192.

Research output: Contribution to journalArticle

Zhang, Hong ; Huang, Huan ; Cali, Ann ; Takvorian, Peter M. ; Feng, Xiaochuan ; Zhou, Ghou ; Weiss, Louis M. / Investigations into microsporidian methionine aminopeptidase type 2 : A therapeutic target for microsporidiosis. In: Folia Parasitologica. 2005 ; Vol. 52, No. 1-2. pp. 182-192.
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