Brucella abortus nicotinamidase (PncA) contributes to its intracellular replication and infectivity in mice
Brucella abortus nicotinamidase (PncA) contributes to its intracellular replication and infectivity in mice
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DOI：
10.1016/j.femsle.2004.03.038
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发表时间：
2004-05-15
影响因子：
2.1
通讯作者：
Watarai, M
中科院分区：
文献类型：
--
作者：
Kim, S;Kurokawa, D;Watarai, M
布鲁氏菌属是兼性的细胞内病原体，具有在专业和非专业吞噬细胞中生存和繁殖的能力，并导致家畜流产和人类波动热。其致病机制和致病因素尚不完全清楚。流产布鲁氏菌烟酰胺酶/吡氨酰胺酶突变体(pncA突变体)不能在HeLa细胞中复制，在巨噬细胞中的细胞内复制速率低于野生型。在HeLa细胞和巨噬细胞中加入烟酸，而不是烟酰胺，可以支持pncA突变体的细胞内复制。PncA突变体既不与晚期内体共定位，也不与溶酶体共定位。流产杆菌VIR B4突变株在4周后从小鼠的脾组织中完全清除，而pncA突变株在10周后从脾组织中分离的细菌数量减少了1.5个对数。尽管pncA突变体在小鼠中显示出毒力降低和细胞内复制缺陷，但其对毒力较强的流产杆菌菌株544的保护能力被完全保留。这些结果表明，pncA不促进流产杆菌在细胞内的运输，但有助于利用细胞内生长所需的营养物质。我们的结果表明，对pncA突变体的详细特征可能有助于改进目前可用的活疫苗。(C)2004年欧洲微生物学会联合会。爱思唯尔出版，版权所有。
Brucella spp. are facultative intracellular pathogens that have the ability to survive and multiply in professional and non-professional phagocytes, and cause abortion in domestic animals and undulant fever in humans. The mechanism and factors of virulence are not fully understood. Nicotinamidase/pyrazinamidase mutant (pncA mutant) of Brucella abortus failed to replicate in HeLa cells, and showed a lower rate of intracellular replication than that of wild-type strain in macrophages. Addition of nicotinic acid, but not nicotinamide, into medium supported intracellular replication of pncA mutant in HeLa cells and macrophages. The pncA mutant was not co-localizing with either late endosomes or lysosomes. The B. abortus vir B4 mutant was completely cleared from the spleens of mice after 4 weeks, while the pncA mutant showed a 1.5-log reduction of the number of bacteria isolated from spleens after 10 weeks. Although pncA mutant showed reduced virulence in mice and defective intracellular replication, its ability to confer protection against the virulent B. abortus strain 544 was fully retained. These results suggest that PncA does not contribute to intracellular trafficking of B. abortus, but contributes to utilization of nutrients required for intracellular growth. Our results indicate that detailed characterizations of the pncA mutant may help the improvement of currently available live vaccines. (C) 2004 Federation of European Microbiological Societies. Published by Elsevier B.V. All rights reserved.