A blasticidin S-resistant Plasmodium falciparum mutant with a defective plasmodial surface anion channel
A blasticidin S-resistant Plasmodium falciparum mutant with a defective plasmodial surface anion channel
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DOI：
10.1073/pnas.0610353104
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发表时间：
2007-01-16
影响因子：
11.1
通讯作者：
Desai, Sanjay A.
中科院分区：
文献类型：
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作者：
Hill, David A.;Pillai, Ajay D.;Desai, Sanjay A.
感染疟原虫的红细胞对有机和无机溶质的渗透性显著增加。疟原虫表面阴离子通道（PSAC），一种不寻常的电压依赖性离子通道感染后诱导的主机膜上，可能在这些渗透性的变化中发挥核心作用。在这里，我们通过杀稻瘟菌素S体外筛选鉴定了一个功能性PSAC突变体。在培养过程中产生了对杀稻瘟菌素S的抗性，并与对多种溶质的渗透性显著降低相关，这与通过共同途径摄取一致。单通道记录显示PSAC门控的显着变化，增加了一个亚电导状态不存在于野生型通道。通道的选择性和药理学也发生了显着变化。最终损失的突变体表型后，删除的选择压力和生长较慢的突变体寄生虫表明，PSAC在细胞内寄生虫的生存发挥重要作用。这些发现为通过PSAC摄取不同的溶质提供了坚实的证据，并暗示了一个或多个寄生虫基因在该通道的表达中。
Erythrocytes infected with malaria parasites exhibit marked increases in permeability to organic and inorganic solutes. The plasmodial surface anion channel (PSAC), an unusual voltage-dependent ion channel induced on the host membrane after infection, may play a central role in these permeability changes. Here, we identified a functional PSAC mutant through in vitro selection with blasticidin S. Resistance to blasticidin S was generated during culture and correlated with significant reductions in permeability to multiple solutes, consistent with uptake via a common pathway. Single channel recordings revealed marked changes in PSAC gating with the addition of a subconductance state not present in wild-type channels. The channel's selectivity profile and pharmacology also were significantly altered. Eventual loss of the mutant phenotype upon removal of selective pressure and slower growth of mutant parasites suggest that PSAC serves an important role in intracellular parasite survival. These findings provide solid evidence for the uptake of diverse solutes via PSAC and implicate one or more parasite genes in expression of this channel.