D'Enfert C, Diaquin M, Delit A, Wuscher N, Debeaupuis J P, Huerre M, Latge J P
Laboratoire des Aspergillus and Unité d'Histopathologie, Institut Pasteur, Paris, France.
Infect Immun. 1996 Oct;64(10):4401-5. doi: 10.1128/iai.64.10.4401-4405.1996.
Aspergillus fumigatus mutants that are deficient in the de novo UMP biosynthesis pathway because of a mutation in the pyrG gene encoding orotidine-5'-phosphate decarboxylase (and therefore auxotrophic for uridine or uracil) were evaluated in a murine model of invasive aspergillosis. These mutants were entirely nonpathogenic, and mutant conidia remained ungerminated in alveolar macrophages. Both the germination and virulence defects could be restored by supplementing the drinking water of the animals with uridine. DNA-mediated transformation of one of the pyrG mutants with the Aspergillus niger pyrG gene also restored virulence. These results suggest that uridine and uracil are limiting in the lung environment, thus preventing conidium germination and hence virulence of the pyrG mutants.
由于编码乳清苷 -5'-磷酸脱羧酶的pyrG基因突变而导致从头UMP生物合成途径缺陷的烟曲霉突变体（因此对尿苷或尿嘧啶营养缺陷），在侵袭性曲霉病的小鼠模型中进行了评估。这些突变体完全无致病性，并且突变体分生孢子在肺泡巨噬细胞中仍未萌发。通过在动物饮水中补充尿苷，可以恢复萌发和毒力缺陷。用黑曲霉pyrG基因对其中一个pyrG突变体进行DNA介导的转化也恢复了毒力。这些结果表明，尿苷和尿嘧啶在肺环境中是有限的，从而阻止了分生孢子的萌发，进而阻止了pyrG突变体的毒力。
