Effect of a bis-benzyl polyamine analogue on Pneumocystis carinii.
Effect of a bis-benzyl polyamine analogue on Pneumocystis carinii.
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双苄基多胺类似物对卡氏肺孢子虫的作用。
DOI：
10.1128/aac.44.2.337-343.2000
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发表时间：
2000
影响因子：
4.9
通讯作者：
ClarksonJr,AB
中科院分区：
文献类型：
--
作者：
Merali,S;Saric,M;Chin,K;ClarksonJr,AB
Pneumocystis cariniiis the causative agent ofP. cariniipneumonia (PCP), an opportunistic infection associated with AIDS and other immunosuppressed conditions. Although polyamine metabolism of this fungus has been shown to be a chemotherapeutic target, this metabolism has not been thoroughly investigated. Reported here is the effect of one polyamine analogue,N,N′-bis{3-[(phenylmethyl)amino]propyl}-1,7-diaminoheptane (BBS), onP. carinii. BBS inhibits the growth ofP. cariniiin culture, but at concentrations higher than those required to inhibit the growth of other pathogens. However, BBS is at least as active in an animal model of PCP as in other models of diseases studied. BBS causes some reduction inP. cariniipolyamine content and polyamine biosynthetic enzyme activities, but the effect is less than that observed with other pathogens and very much less than the effect of the polyamine biosynthesis inhibitordl-α-difluoromethylornithine. BBS entersP. cariniicells via a polyamine transporter, unlike all other cells that have been studied.P. cariniicells do not remove the benzyl groups of BBS, as is reported for mammalian cells. The most likely mode of action is displacement of natural polyamines. Overall, the activity of BBS provides further evidence that polyamines and polyamine metabolism are rational targets for the development of drugs to treat PCP. Because the details of BBS-P. cariniiinteraction differ from those of other cells studied, polyamine analogues may provide a highly specific treatment for PCP.
