In vitro efficacy of nikkomycin Z against the human isolate of the microsporidian species Encephalitozoon hellem

Since 1985 microsporidia have been recognized as a cause of emerging infect ions in humans, mainly in immunocompromised human immunodeficiency virus-po sitive subjects. As chitin is a basic component of the microsporidian infec tive stage, the spore, we evaluated in vitro the susceptibility of a human- derived strain of Encephalitozoon hellem to nikkomycin Z, a peptide-nucleos ide antibiotic known as a competitive inhibitor of chitin synthase enzymes. Transmission electron microscopy showed that this drug; at 25 mug/ml, redu ced the number of parasitic foci by about 35% +/- standard deviation after 7 days of culture (P < 0.0001) and induced cell damage of both mature and i mmature spores and also other sporogonic and merogonic stages. In particula r, an irregular outline of the cell shape and an abnormally condensed cytop lasm in meronts and sporonts were documented. Also, the polar tubule and th e polaroplast membranes appeared disarrayed in the sporoblast stage. The sp ore wall showed an enlarged endospore and delaminated exospore. Mature spor es had a complete cytoplasmic disorganization and a swollen and delaminated cell wall. No ultrastructural cell damage was observed in uninfected contr ol cultures treated with the drug.