In-vitro activity of lytic peptides alone and in combination with macrolides and inhibitors of dihydrofolate reductase against Pneumocystis carinii.

Abstract

The in-vitro activity of cecropin P1, magainin II, indolicidin and ranalexin alone and in combination with macrolides and dihydrofolate reductase inhibitors (DHFRs) was investigated against six clinical isolates of Pneumocystis carinii. The susceptibility tests were performed by inoculation of the isolates on to cell monolayers and determining the parasite count after 72 h incubation at 37 degrees C. The culture medium was supplemented with serial dilutions of each agent. The four peptides suppressed the growth of cysts and trophozoites by > or = 50% at 20 microM and 2 microM, respectively, with the exception of indolicidin (cysts: IC50, 20 microM; trophozoites: IC50, 20 microM). The IC90 values of all peptides for either cysts or trophozoites were observed at a concentration of 20 microM. Our data showed that the activity of lytic peptides remained virtually unchanged when they were tested either alone or in combination with macrolides and DHFRs, with the exception of ranalexin: a cysts/trophozoites reduction in the range 77.3-85.1% was observed when ranalexin 2 microM was combined with 4 mg/L of macrolides. Our study suggests that lytic peptides may be effective in inhibiting the growth of P. carinii in vitro. In addition some of these compounds seem to have an effective interaction with hydrophobic antibiotics.