Fungicidal properties of defensin NP-1 and activity against Cryptococcus neoformans in vitro.

AUTOR(ES)

Alcouloumre, M S

RESUMO

Defensin NP-1, derived from the neutrophils of rabbits, was tested for its fungistatic and fungicidal activity against strains of Cryptococcus neoformans. The MICs for the encapsulated strains tested ranged from 3.75 to 15.0 micrograms of NP-1 per ml. The minimum fungicidal concentrations for these strains were similar to the MICs. An acapsular strain, however, had a lower MIC of 0.93 and minimum fungicidal concentration of 1.88 micrograms/ml. NP-1 demonstrated time-dependent and concentration-dependent killing of C. neoformans. Killing occurred rapidly in the first 20 min of exposure to NP-1 and was maximum at 90 to 120 min. Killing of C. neoformans by NP-1 was concentration dependent with 31% +/- 9% survival at 25 micrograms/ml, 13% +/- 4% survival at 50 micrograms/ml, 9% +/- 5% survival at 75 micrograms/ml, and 5% +/- 3% survival at 100 micrograms/ml. NP-1's fungicidal effect on C. neoformans was also inoculum dependent, with increased activity observed at 10(4) versus 10(5) or 10(6) cells per ml. In addition, stationary-phase C. neoformans was less susceptible to NP-1 killing than yeast cells in the logarithmic phase. Subinhibitory concentrations of both NP-1 (0.25 x MIC) and fluconazole (0.25 x MIC) acted synergistically in inhibiting growth of C. neoformans. Similar combinations of NP-1 and amphotericin B, however, did not yield synergy.

Documentos Relacionados

• Eosinophil-Cryptococcus neoformans interactions in vivo and in vitro.
• In Vitro and In Vivo Activity of a Synthetic Halogenated Quinoline Against Cryptococcus neoformans
• Pneumocandin L-743,872 enhances the activities of amphotericin B and fluconazole against Cryptococcus neoformans in vitro.
• Fungicidal mechanism of action of D0870 against Cryptococcus neoformans under acidic conditions.
• In vitro evaluation of combination of fluconazole and flucytosine against Cryptococcus neoformans var. neoformans.