Auxotrophs of Plasmodium falciparum dependent on p-aminobenzoic acid for growth.

The isolation of auxotrophic strains of a parasite offers new opportunities for studying parasitology. We have isolated cloned lines of Plasmodium falciparum that, unlike the parent line from which they were derived, rely on exogenous p-aminobenzoic acid (PABA) for growth. Isolation involved random mutagenesis of a cloned line of P. falciparum and subsequent selection of PABA-dependent parasites. Both parent and PABA-dependent clones were analyzed for PABA uptake and synthesis. Each clone takes up comparable amounts of PABA from the medium. The parent line, clone 3D7, can synthesize PABA de novo, whereas the PABA-dependent clones cannot. The requirement of exogenous PABA for growth by the auxotrophic strains coupled with their inability to synthesize PABA indicates that normal parasite growth can be completely supported by either synthesis or salvage. This work further clarifies the relationship between the availability of PABA and success of the parasite, an issue of debate from classic studies showing reduced parasite load in individuals on milk-fed diets.

寄生虫营养缺陷型菌株的分离，为寄生虫学研究提供了全新的契机。我们成功分离得到数株恶性疟原虫（Plasmodium falciparum）的克隆株系，与衍生它们的亲本株系不同，这些克隆株系的生长依赖外源性对氨基苯甲酸（p-aminobenzoic acid, PABA）。本次分离流程包括对一株恶性疟原虫克隆株系进行随机诱变，后续再筛选出依赖PABA的寄生虫株。我们对亲本株系与依赖PABA的克隆株均开展了PABA摄取与合成相关分析，结果显示所有克隆株均可从培养基中摄取等量的PABA。亲本株系3D7可从头合成PABA，而依赖PABA的克隆株则不具备该合成能力。这些营养缺陷型菌株的生长需要外源性PABA，且无法自主合成PABA，这一结果表明，寄生虫的正常生长可通过从头合成PABA，或是通过补救途径摄取外源PABA两种方式得以完全保障。本研究进一步阐明了PABA可用性与寄生虫增殖能力之间的关联——此前经典研究发现，以牛乳为食的个体体内寄生虫载量降低，该问题此前尚存争议。