Alcouloumre M S, Ghannoum M A, Ibrahim A S, Selsted M E, Edwards J E
Division of Infectious Diseases, St. John's Cardiovascular Research Center, LAC-Harbor UCLA Medical Center, University of California-Los Angeles School of Medicine, Torrance 90509.
Antimicrob Agents Chemother. 1993 Dec;37(12):2628-32. doi: 10.1128/AAC.37.12.2628.
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.
对源自兔中性粒细胞的防御素NP-1，检测了其对新型隐球菌菌株的抑菌和杀菌活性。所检测的有荚膜菌株的最低抑菌浓度（MIC）为每毫升3.75至15.0微克NP-1。这些菌株的最低杀菌浓度与最低抑菌浓度相似。然而，一株无荚膜菌株的最低抑菌浓度较低，为0.93微克/毫升，最低杀菌浓度为1.88微克/毫升。NP-1对新型隐球菌的杀灭表现出时间依赖性和浓度依赖性。在接触NP-1的最初20分钟内杀灭迅速发生，在90至120分钟时达到最大值。NP-1对新型隐球菌的杀灭呈浓度依赖性，在25微克/毫升时存活率为31%±9%，在50微克/毫升时存活率为13%±4%，在75微克/毫升时存活率为9%±5%，在100微克/毫升时存活率为5%±3%。NP-1对新型隐球菌的杀菌作用也与接种量有关，每毫升10⁴个细胞时观察到的活性高于10⁵或10⁶个细胞时。此外，稳定期的新型隐球菌比对数期的酵母细胞对NP-1的杀灭更不敏感。NP-1（0.25×MIC）和氟康唑（0.25×MIC）的亚抑菌浓度在抑制新型隐球菌生长方面具有协同作用。然而，NP-1和两性霉素B的类似组合并未产生协同作用。
