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 transport system inhibitors and two polyether ionophores was investigated against four clinical isolates of Pneumocystis carinii recovered from bronchoalveolar lavages of AIDS patients. The susceptibility tests were performed by inoculating 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 Dulbecco's modified Eagle's medium containing serial dilutions of cecropin P1, magainin II, benzamil, 5-(Nmethyl-Nisobutyl)amiloride (MIBA), lasalocid and nigericin. The two vertebrate lytic peptides showed high activity against trophozoites and 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, while 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 IC50s of benzamil and MIBA were observed at the highest concentrations tested, 35.62 and 29.98 mg/L, respectively. However, 90% inhibition was not achieved. Lasalocid and nigericin at 0.05 mg/L gave inhibition comparable to that observed with the highest tested concentrations of cecropin P1 and magainin II, but significant injury to the cell monolayer 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 and trophozoite counts, respectively. Our results suggest that lytic peptides and lasalocid may be effective in inhibiting P. carinii growth at concentrations which are not toxic for the cell monolayer.
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Institute of Infectious Diseases and Public Health, University of Ancona, Italy. cmalinif@popcsi.unian.it
Giacometti
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Barchiesi
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Scalise
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D017088:AIDS-Related Opportunistic Infections / Q000382:microbiology; D000584:Amiloride / Q000031:analogs & derivatives / Q000494:pharmacology; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D000890:Anti-Infective Agents / Q000494:pharmacology*; D023181:Antimicrobial Cationic Peptides; D006801:Humans; D017136:Ion Transport / Q000187:drug effects; D007476:Ionophores / Q000494:pharmacology*; D054806:Magainins; D008826:Microbial Sensitivity Tests; D010455:Peptides / Q000494:pharmacology*; D011010:Pneumocystis / Q000187:drug effects* / Q000378:metabolism; D011020:Pneumonia, Pneumocystis / Q000382:microbiology; D029867:Xenopus Proteins
D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents; D023181:Antimicrobial Cationic Peptides; D007476:Ionophores; D054806:Magainins; D010455:Peptides; D029867:Xenopus Proteins; C013407:benzamil; C053301:magainin 2 peptide, Xenopus; D000584:Amiloride; C070016:cecropin P1-LI