Characterization of the galU gene of Streptococcus pneumoniae encoding a uridine diphosphoglucose pyrophosphorylase: a gene essential for capsular polysaccharide biosynthesis.

Characterization of the galU gene of Streptococcus pneumoniae encoding a uridine diphosphoglucose pyrophosphorylase: a gene essential for capsular polysaccharide biosynthesis.
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DOI:
10.1084/jem.188.11.2047
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发表时间:
1998-12-07
期刊:
The Journal of experimental medicine
影响因子:
--
通讯作者:
García E
García E
中科院分区:
其他
文献类型:
--
作者:
Mollerach M;López R;García E

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肺炎链球菌Galu基因已被克隆和测序。含有重组质粒pMMG2(Galu)的大肠杆菌细胞过量表达一种蛋白,该蛋白对应于一种尿苷5‘-三磷酸:葡萄糖-1-磷酸尿苷转移酶(UDP-GLC焦磷酸化酶),该酶负责合成UDP-GLC,UDP-GLC是多糖生物合成中的关键化合物。在化脓性链球菌基因组的部分核苷酸序列中发现了与肺炎链球菌Galu非常相似的基因。1型肺炎球菌的Galu基因敲除突变体无法合成可检测到的胶囊。在3型肺炎链球菌细胞中也发现了相同的结果,尽管这些细菌包含一个类型特定的基因(Cap3C),该基因也编码UDP-Glc焦磷酸化酶。由于真核细胞中的UDP-Glc焦磷酸化酶似乎与原核生物完全无关,我们推测GalU可能是寻找控制肺炎球菌和化脓性链球菌等细菌致病性的新药的合适靶点。
The galU gene of Streptococcus pneumoniae has been cloned and sequenced. Escherichia coli cells harboring the recombinant plasmid pMMG2 (galU) overproduced a protein that has been shown to correspond to a uridine 5′-triphosphate:glucose-1-phosphate uridylyltransferase (uridine diphosphoglucose [UDP-Glc] pyrophosphorylase) responsible for the synthesis of UDP-Glc, a key compound in the biosynthesis of polysaccharides. A gene very similar to the S. pneumoniae galU has been found in a partial nucleotide sequence of the Streptococcus pyogenes genome. Knockout galU mutants of type 1 pneumococci are unable to synthesize a detectable capsule. An identical result was found in type 3 S. pneumoniae cells in spite of the fact that these bacteria contain a type-specific gene (cap3C) that also encodes a UDP-Glc pyrophosphorylase. Since eukaryotic UDP-Glc pyrophosphorylases appear to be completely unrelated to their prokaryotic counterparts, we postulate that GalU may be an appropriate target for the search of new drugs to control the pathogenicity of bacteria like pneumococcus and S. pyogenes.