IN-VITRO ACTIVITY OF LYTIC PEPTIDES ALONE AND IN COMBINATION WITH MACROLIDES AND INHIBITORS OF DIHYDROFOLATE-REDUCTASE AGAINST PNEUMOCYSTIS-CARINII

The in-vitro activity of cecropin P1, magainin II, indolicidin and ran alexin alone and in combination with macrolides and dihydrofolate redu ctase inhibitors (DHFRs) was investigated against six clinical isolate s 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 medi um was supplemented with serial dilutions of each agent. The four pept ides suppressed the growth of cysts and trophozoites by greater than o r equal to 50% at 20 mu M and 2 mu M, respectively, with the exception of indolicidin (cysts: IC50, 20 mu M; trophozoites: IC50, 20 mu M). T he IC90 values of all peptides for either cysts or trophozoites were o bserved at a concentration of 20 mu M. Our data showed that the activi ty of lytic peptides remained virtually unchanged when they were teste d either alone or in combination with macrolides and DHFRs, with the e xception of ranalexin: a cysts/trophozoites reduction in the range 77. 3-85.1% was observed when ranalexin 2 mu M was combined with 4 mg/L of macrolides. Our study suggests that lytic peptides may be effective i n inhibiting the growth of P. carinii in vitro. In addition some of th ese compounds seem to have an effective interaction with hydrophobic a ntibiotics.