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Role of Purine Biosynthesis in Bacillus anthracis Pathogenesis and Virulence

机译：嘌呤生物合成在炭疽芽孢杆菌的发病机理和毒力中的作用

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Bacillus anthracis, the etiological agent of anthrax, is a spore-forming, Gram-positive bacterium and a category A biothreat agent. Screening of a library of transposon-mutagenized B. anthracis spores identified a mutant displaying an altered phenotype that harbored a mutated gene encoding the purine biosynthetic enzyme PurH. PurH is a bifunctional protein that catalyzes the final steps in the biosynthesis of the purine IMP. We constructed and characterized defined purH mutants of the virulent B. anthracis Ames strain. The virulence of the purH mutants was assessed in guinea pigs, mice, and rabbits. The spores of the purH mutants were as virulent as wild-type spores in mouse intranasal and rabbit subcutaneous infection models but were partially attenuated in a mouse intraperitoneal model. In contrast, the purH mutant spores were highly attenuated in guinea pigs regardless of the administration route. The reduced virulence in guinea pigs was not due solely to a germination defect, since both bacilli and toxins were detected in vivo, suggesting that the significant attenuation was associated with a growth defect in vivo. We hypothesize that an intact purine biosynthetic pathway is required for the virulence of B. anthracis in guinea pigs.
机译：炭疽杆菌是炭疽的病原体，是一种形成芽孢的革兰氏阳性细菌，是A类生物威胁剂。转座子诱变的炭疽芽孢杆菌孢子文库的筛选确定了一个突变体，该突变体表现出改变的表型，该突变体具有编码嘌呤生物合成酶PurH的突变基因。 PurH是一种双功能蛋白，可催化嘌呤IMP生物合成的最终步骤。我们构建并鉴定了强毒炭疽杆菌Ames菌株的purH突变体。在豚鼠，小鼠和兔子中评估了purH突变体的毒力。在小鼠鼻内和兔子皮下感染模型中，purH突变体的孢子与野生型孢子一样强，但在小鼠腹膜模型中部分减毒。相反，在豚鼠中，不管施用途径如何，purH突变体的孢子都高度减毒。豚鼠的致病力降低不仅是由于发芽缺陷引起的，因为在体内可检测到细菌和毒素，这表明明显的减毒与体内生长缺陷有关。我们假设完整的嘌呤生物合成途径是豚鼠中炭疽芽孢杆菌的毒力所必需的。

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