Formate acts as a diffusible signal to induce Salmonella invasion
Formate acts as a diffusible signal to induce Salmonella invasion
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DOI：
10.1128/jb.00205-08
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发表时间：
2008-06-01
影响因子：
3.2
通讯作者：
Altier, Craig
中科院分区：
文献类型：
--
作者：
Huang, Yanyan;Suyemoto, Mitsu;Altier, Craig
为了感染动物宿主，鼠伤寒沙门氏菌必须穿透肠上皮屏障。这种入侵过程需要沙门氏菌致病岛I（SPI 1）内编码的III型分泌系统。我们发现，一个突变体的乙酸激酶和磷酸转乙酰酶基因（ackA-pta）的缺失是缺乏入侵和SPI 1的表达，但入侵基因的表达被完全恢复，通过提供由野生型菌株的生长条件培养基，这表明由野生型产生的信号，但不是由ackA-pta突变体，是入侵所必需的。该突变体还向培养基中分泌了68倍的甲酸盐，并且向培养物中加入甲酸钠恢复了突变体的SPI 1表达和对培养的上皮细胞的侵袭。甲酸盐的作用依赖于pH值，需要pH值低于中性，小鼠研究表明，远端回肠（沙门氏菌在该物种中入侵的首选部位）具有适当的甲酸盐浓度和pH值以引发入侵，而盲肠不含可检测到的甲酸盐。此外，我们发现甲酸盐影响SPI 1、hilA和hilD的主要调节因子，但甲酸盐代谢的主要途径对其信号活性没有发挥作用。
To infect an animal host, Salmonella enterica serovar Typhimurium must penetrate the intestinal epithelial barrier. This process of invasion requires a type III secretion system encoded within Salmonella pathogenicity island I (SPI1). We found that a mutant with deletions of the acetate kinase and phosphotransacetylase genes (ackA-pta) was deficient in invasion and SPI1 expression but that invasion gene expression was completely restored by supplying medium conditioned by growth of the wild-type strain, suggesting that a signal produced by the wild type, but not by the ackA-pta mutant, was required for invasion. This mutant also excreted 68-fold-less formate into the culture medium, and the addition of sodium formate to cultures restored both the expression of SPI1 and the invasion of cultured epithelial cells by the mutant. The effect of formate was pH dependent, requiring a pH below neutrality, and studies in mice showed that the distal ileum, the preferred site of Salmonella invasion in this species, had the appropriate formate concentration and pH to elicit invasion, while the cecum contained no detectable formate. Furthermore, we found that formate affected the major regulators of SPI1, hilA and hilD, but that the primary routes of formate metabolism played no role in its activity as a signal.