Nagle D P, Teal R, Eisenbraun A
J Bacteriol. 1987 Sep;169(9):4119-23. doi: 10.1128/jb.169.9.4119-4123.1987.
Growth of Methanobacterium thermoautotrophicum Marburg is inhibited by the pyrimidine, 5-fluorouracil (FU). It was shown previously that methanogenesis is not inhibited to the same extent as growth. A spontaneously occurring FU-resistant strain (RTAE-1) was isolated from a culture of strain Marburg. The growth of both strains was inhibited by 5-fluorodeoxyuridine but not 5-fluorocytosine, and the wild type was more susceptible to inhibition by 5-azauracil and 6-azauracil than was strain RTAE-1. The cellular targets for the pyrimidine analogs are not known. When the accumulation of 14C-labeled uracil or FU by the two strains was compared, the wild type took up 15-fold more radiolabel per cell than did the FU-resistant strain. In the wild type, radiolabel from uracil was incorporated into the soluble pool, RNA, and DNA. The metabolism of uracil appeared to involve a uracil phosphoribosyltransferase activity. Strain Marburg extracts contained this enzyme, whereas FU-resistant strain RTAE-1 extracts had less than 1/10 as much activity. Although it is possible that a change in permeability to the compounds plays a role in the stable resistance of strain RTAE-1, the fact that it lacks the ability to metabolize pyrimidines to nucleotides is sufficient to account for its phenotype.
嗜热自养甲烷杆菌马尔堡菌株（Methanobacterium thermoautotrophicum Marburg）的生长受到嘧啶5-氟尿嘧啶（FU）的抑制。先前已表明，甲烷生成的受抑制程度不如生长受抑制程度大。从马尔堡菌株的培养物中分离出一株自发产生的FU抗性菌株（RTAE-1）。两种菌株的生长均受到5-氟脱氧尿苷的抑制，但不受5-氟胞嘧啶的抑制，并且野生型比RTAE-1菌株对5-氮杂尿嘧啶和6-氮杂尿嘧啶的抑制更敏感。嘧啶类似物的细胞靶点尚不清楚。当比较两种菌株对14C标记的尿嘧啶或FU的积累时，野生型每个细胞摄取的放射性标记比FU抗性菌株多15倍。在野生型中，尿嘧啶的放射性标记被掺入可溶性池、RNA和DNA中。尿嘧啶的代谢似乎涉及尿嘧啶磷酸核糖基转移酶活性。马尔堡菌株提取物含有这种酶，而FU抗性菌株RTAE-1提取物的活性不到其1/10。虽然化合物通透性的变化可能在RTAE-1菌株的稳定抗性中起作用，但它缺乏将嘧啶代谢为核苷酸的能力这一事实足以解释其表型。
