Growth phase-regulated induction of Salmonella-induced macrophage apoptosis correlates with transient expression of SPI-1 genes
Growth phase-regulated induction of Salmonella-induced macrophage apoptosis correlates with transient expression of SPI-1 genes
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DOI：
10.1128/jb.181.11.3433-3437.1999
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发表时间：
1999-06-01
影响因子：
3.2
通讯作者：
Baccarini, M
中科院分区：
文献类型：
--
作者：
Lundberg, U;Vinatzer, U;Baccarini, M
据报道，侵袭性沙门氏菌在感染后2至14小时内通过沙门氏菌致病性岛1 （SPI-1）编码的III型分泌机制诱导部分被感染的巨噬细胞凋亡。在这里，我们发现从对数期过渡到固定期的细菌导致90%的巨噬细胞在感染后30至60分钟内发生与吞噬无关的caspase介导的凋亡。沙门氏菌诱导这种快速凋亡的能力受到生长阶段的调节和细胞类型的限制，上皮细胞具有抗性。通过破坏hilA基因（编码SPI-1基因的调节因子）和表达组成型活性PhoPQ，细胞凋亡诱导也被取消。hilA本身和SPI-1基因亚群在液体培养基中有氧生长时短暂表达。然而，有趣的是，发现hilA仅在prgH基因的表达中是必需的，而sipB、invA和invF则以hilA独立的方式表达。SPI-1基因的表达和侵袭相关蛋白的分泌与细胞凋亡的诱导有时间相关性，并可能代表其分子基础。因此，生长阶段的转变调节了毒力决定因子的表达和分泌，代表了迄今为止报道的诱导细胞凋亡的最有效的环境线索。
Invasive Salmonella has been reported to induce apoptosis in a fraction of infected macrophages within 2 to 14 h from the time of infection by a mechanism involving the type III secretion machinery encoded by the Salmonella pathogenicity island 1 (SPI-1), Here, we show that bacteria in the transition from logarithmic to stationary phase cause 90% of the macrophages to undergo phagocytosis independent, caspase-mediated apoptosis,within 30 to 60 min of infection, The ability of Salmonella to induce this rapid apoptosis was growth phase regulated and cell type restricted, with epithelial cells being resistant. Apoptosis induction was also abrogated by disruption of the hilA gene (encoding a regulator of SPI-1 genes) and by the expression of a constitutively active PhoPQ. hilA itself and a subset of SPI-1 genes were transiently expressed during aerobic growth in liquid medium. Interestingly, however, hilA was found to be required only for the expression of the prgH gene, while sipB, invA, and invF were expressed in a hilA-independent manner. The expression of SPI-1 genes and the secretion of invasion-associated proteins correlated temporally with the induction of apoptosis and are likely to represent its molecular basis. Thus, growth phase transition regulates the expression and secretion of virulence determinants and represents the most efficient environmental cue for apoptosis induction reported to date.