Inhibition of microsporidia growth in vitro.

Important note: Information in this article was accurate in 2000. The state of the art may have changed since the publication date.

Inhibition of microsporidia growth in vitro.

Abstr Gen Meet Am Soc Microbiol. 1999 May 30-Jun 3;99:11 (abstract no. A-52). Unique Identifier : AIDSLINE AIDS/20712023
Didier ES; Bertucci DC; Leblanc L; Tulane Regional Primate Research Center, Covington, LA.

Abstract: Microsporidia are parasites that cause opportunistic infections in persons with AIDS and organ transplant recipients. No universally effective treatment exists. Although fumagillin is effective against microsporidiosis in honeybees, inhibits microsporidia in tissue culture, and is effective when used topically to treat ocular microsporidial infections, it is too toxic for systemic rise. An in vitro system utilizing Encephalitozoon intestinalis (Ei) and Vittaforma corneae (Vc) was utilized to determine if fumagillin-related compounds would inhibit the growth of microsporidia, and an MTT assay was used to assess host cell toxicity. The fumagillin analogue, TNP-470, previously was found to inhibit growth of the microsporidia by greater than 80% at non-toxic doses and the TCID50 values were calculated at 0.87 nM and 0.94 nM against Ei and Vc, respectively. Six ovalicin derivatives, which are structurally related to fumagillin, were assayed in this system and expressed TCID50 values below 10 micromolar against both microsporidians at non-toxic doses. Since fumagillin has shown antiangiogenesis activity, the angiogenesis inhibitors alginic acid, genistein, minocycline, 1,10 phenanthroline, suramin, doxycycline HCl, and all trans retinol were assayed, but these compounds failed to significantly inhibit growth of the microsporidia at non-toxic doses. Fumagillin also appears to be a protease inhibitor, so members of various groups of protease inhibitors were assayed. Two serine protease inhibitors, PMSF and APMSF, inhibited both microsporidians by 70% or more at non-toxic doses. Several zinc-dependant metalloprotease inhibitors failed to inhibit the microsporidia, with the exception of tissue inhibitor of metalloprotease 2 (TIMP-2) which inhibited Vc by more than 80% at non-toxic doses in vitro. These results suggest that studies continue on the fumagillin-related compounds for finding antimicrosporidial drugs and that serine proteases also may be useful drug targets.

Keywords: ABSTRACT Angiogenesis Inhibitors/*PHARMACOLOGY Antiprotozoal Agents/*PHARMACOLOGY Fatty Acids, Unsaturated/*PHARMACOLOGY Microsporida/*DRUG EFFECTS/GROWTH & DEVELOPMENT
000730
A0070911

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