Polyamines are required for virulence in Salmonella enterica serovar Typhimurium.
Polyamines are required for virulence in Salmonella enterica serovar Typhimurium.
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DOI：
10.1371/journal.pone.0036149
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Olsen JE
中科院分区：
文献类型：
--
作者：
Jelsbak L;Thomsen LE;Wallrodt I;Jensen PR;Olsen JE
对环境信号的感知和反应是细菌生理学和毒力的基本特征。在这里，我们确定了多胺作为新的环境信号的肠道沙门氏菌血清型鼠伤寒沙门氏菌，一个主要的细胞内病原体和伤寒研究的模式生物的毒力必不可少。其毒力的核心是两个主要的毒力位点沙门氏菌致病岛1和2（SPI1和SPI2）。SPI1促进上皮细胞的侵袭，而SPI2使S.鼠伤寒沙门氏菌在宿主细胞内的专门区室中存活和增殖。在这项研究中，我们表明，一个S。鼠伤寒多胺突变体在侵袭、细胞内存活、杀死线虫以及伤寒小鼠模型的全身感染方面存在缺陷。突变体的毒力可以通过遗传互补来恢复，并且入侵和细胞内存活也可以通过在感染前向细菌培养物中添加外源腐胺和亚精胺来补充。有趣的是，通过在感染前向细菌培养物中加入外源腐胺和亚精胺，多胺突变体的细胞内存活率显著高于野生型水平，表明这些多胺作为引发S的环境信号起作用。鼠伤寒沙门氏菌的细胞内存活。因此，在阐明这些多胺在感染中的作用的实验表明，从两个主要的毒力基因座SPI1和SPI2的基因的表达响应于外源多胺，并减少在多胺突变体。总之，我们的数据表明，腐胺和亚精胺在控制S.鼠伤寒沙门氏菌最可能通过刺激基本毒力基因座的表达。此外，我们的数据暗示这些多胺作为关键信号在S。鼠伤寒毒力。
Sensing and responding to environmental cues is a fundamental characteristic of bacterial physiology and virulence. Here we identify polyamines as novel environmental signals essential for virulence of Salmonella enterica serovar Typhimurium, a major intracellular pathogen and a model organism for studying typhoid fever. Central to its virulence are two major virulence loci Salmonella Pathogenicity Island 1 and 2 (SPI1 and SPI2). SPI1 promotes invasion of epithelial cells, whereas SPI2 enables S. Typhimurium to survive and proliferate within specialized compartments inside host cells. In this study, we show that an S. Typhimurium polyamine mutant is defective for invasion, intracellular survival, killing of the nematode Caenorhabditis elegans and systemic infection of the mouse model of typhoid fever. Virulence of the mutant could be restored by genetic complementation, and invasion and intracellular survival could, as well, be complemented by the addition of exogenous putrescine and spermidine to the bacterial cultures prior to infection. Interestingly, intracellular survival of the polyamine mutant was significantly enhanced above the wild type level by the addition of exogenous putrescine and spermidine to the bacterial cultures prior to infection, indicating that these polyamines function as an environmental signal that primes S. Typhimurium for intracellular survival. Accordingly, experiments addressed at elucidating the roles of these polyamines in infection revealed that expression of genes from both of the major virulence loci SPI1 and SPI2 responded to exogenous polyamines and was reduced in the polyamine mutant. Together our data demonstrate that putrescine and spermidine play a critical role in controlling virulence in S. Typhimurium most likely through stimulation of expression of essential virulence loci. Moreover, our data implicate these polyamines as key signals in S. Typhimurium virulence.
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影响因子：
3.2
作者：
GUTNICK, D;CALVO, JM;AMES, BN
通讯作者：
AMES, BN
影响因子：
4.8
作者：
Higashi, K;Kashiwagi, K;Igarashi, K
通讯作者：
Igarashi, K
影响因子：
3.6
作者：
Bajaj, V;Lucas, RL;Lee, CA
通讯作者：
Lee, CA
影响因子：
3.2
作者：
CHANG, ACY;COHEN, SN
通讯作者：
COHEN, SN
DOI：
10.1073/pnas.120163297
发表时间：
2000-06-06
影响因子：
11.1
作者：
Datsenko, KA;Wanner, BL
通讯作者：
Wanner, BL