Sialic acid metabolism and systemic pasteurellosis
Sialic acid metabolism and systemic pasteurellosis
复制标题
DOI：
10.1128/iai.73.3.1284-1294.2005
复制
发表时间：
2005-03-01
影响因子：
3.1
通讯作者：
Vimr, ER
中科院分区：
文献类型：
--
作者：
Steenbergen, SM;Lichtensteiger, CA;Vimr, ER
多杀性巴氏杆菌亚种多杀性病原体是食用动物、野生动物和宠物的寄生性和机会性病原体，也是人类因接触这些动物而感染的人畜共患病原体。在此，对多个血清型A菌株的调查证明了膜唾液酸转移酶的发生。虽然多杀性巴氏杆菌缺乏唾液酸从头合成的两个最早步骤的基因，但向生长培养基中加入唾液酸导致唾液酸的摄取、活化和随后转移到类似脂寡糖的膜受体。两个与大肠杆菌胞苷5 '-单磷酸-N-乙酰神经氨酸合成酶具有同源性的候选激活酶被过量生产为组氨酸标记的多肽。由pm 0187编码的合成酶比pm 1710基因产物的活性高至少37倍，表明pm 0187编码多杀性巴氏杆菌中的初级唾液酸胞苷酰转移酶。在CD-1小鼠系统性巴氏杆菌病模型中，不能启动内化唾液酸异化的唾液酸醛缩酶（pm 1715）突变体没有减弱，表明唾液酸催化剂的营养功能不是系统性疾病所必需的。相反，唾液酸摄取缺陷突变体的衰减支持依赖于唾液酸的环境（宿主）供应的唾液酸化机制在发病机理中的重要作用。综合结果提供了第一个直接的证据，唾液酸化的前体清除机制在巴氏杆菌和一个潜在的三方ATP-独立的周质唾液酸转运蛋白在任何物种。
Pasteurella multocida subsp. multocida is a commensal and opportunistic pathogen of food animals, wildlife, and pets and a zoonotic cause of human infection arising from contacts with these animals. Here, an investigation of multiple serotype A strains demonstrated the occurrence of membrane sialyltransferase. Although P. multocida lacks the genes for the two earliest steps in de novo sialic acid synthesis, adding sialic acid to the growth medium resulted in uptake, activation, and subsequent transfer of sialic acid to a membrane acceptor resembling lipooligosaccharide. Two candidate-activating enzymes with homology to Escherichia coli cytidine 5'-monophospho-N-acetyineuraminate synthetase were overproduced as histidine-tagged polypeptides. The synthetase encoded by pm0187 was at least 37 times more active than the pm1710 gene product, suggesting pm0187 encodes the primary sialic acid cytidylyltransferase in P. multocida. A sialate aldolase (pm1715) mutant unable to initiate dissimilation of internalized sialic acid was not attenuated in the CD-1 mouse model of systemic pasteurellosis, indicating that the nutritional function of sialate catabolism is not required for systemic disease. In contrast, the attenuation of a sialate uptake-deficient mutant supports the essential role in pathogenesis of a sialylation mechanism that is dependent on an environmental (host) supply of sialic acid. The combined results provide the first direct evidence of sialylation by a precursor scavenging mechanism in pasteurellae and of a potential tripartite ATP-independent periplasmic sialate transporter in any species.