IN-VITRO ACTIVITY OF LYTIC PEPTIDES, INHIBITORS OF ION-TRANSPORT SYSTEMS AND IONOPHOROUS ANTIBIOTICS AGAINST PNEUMOCYSTIS-CARINII

The in-vitro activity of two vertebrate lytic peptides, two ion transp ort system inhibitors and two polyether ionophores was investigated ag ainst four clinical isolates of Pneumocystis carinii recovered from br onchoalveolar lavages of AIDS patients. The susceptibility tests were performed by inoculating the isolates on to cell monolayers end determ ining the parasite count after 72 h incubation at 37 degrees C. The cu lture medium was supplemented with Dulbecco's modified Eagle's medium containing serial dilutions of cecropin P1, magainin II, benzamil, 5-( N-methyl-N-isobutyl)amiloride (MIBA), lasalocid and nigericin. The two vertebrate lytic peptides showed high activity against trophozoites a nd cysts. At a concentration of 66.77 mg/L, cecropin P1 produced a 93. 3% and 98.1% reduction in cyst and trophozoite counts, respectively, w hile magainin II at a concentration of 49.33 mg/L produced a 90.6% and 98.7% reduction in cyst and trophozoite counts, respectively. The IC( 50)s of benzamil and MIBA were observed at the highest concentrations tested, 35.62 and 29.98 mg/L, respectively. However, 90% inhibition wa s not achieved. Lasalocid and nigericin at 0.05 mg/L gave inhibition c omparable to that observed with the highest tested concentrations of c ecropin P1 and magainin II, but significant injury to the cell monolay er was also observed when nigericin was tested at this concentration. Lasalocid 0.05 mg/L produced a reduction of 91.3% and 92.0% in cyst an d trophozoite counts, respectively. Our results suggest that lytic pep tides and lasalocid may be effective in inhibiting P. carinii growth a t concentrations which are not toxic far the cell monolayer.