Invasion of HeLa cells by group B streptococcus requires the phosphoinositide-3-kinase signalling pathway and modulates phosphorylation of hostcell Akt and glycogen synthase kinase-3
Invasion of HeLa cells by group B streptococcus requires the phosphoinositide-3-kinase signalling pathway and modulates phosphorylation of hostcell Akt and glycogen synthase kinase-3
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DOI：
10.1099/mic.0.2007/008417-0
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发表时间：
2007-12-01
期刊：
影响因子：
2.8
通讯作者：
Tyrrell, Gregory J.
中科院分区：
文献类型：
--
作者：
Burnham, Carey-Ann D.;Shokoples, Sandra E.;Tyrrell, Gregory J.
The group B streptococcus (GBS) is an opportunistic bacterial pathogen with the ability to cause invasive disease. While the ability of GBS to invade a number of host-cell types has been clearly demonstrated, the invasion process is not well understood at the molecular level. What has been well established is that modulation of host-cell actin microfilaments is essential for GBS invasion to occur. Phosphoinositide-3 kinase (PI3K) is a key regulator of the cytoskeleton in eukaryotic cells. Our goal in this investigation was to explore the role of the PI3K/Akt signalling pathway in epithelial cell invasion by GBS. The epithelial cell invasion process was mimicked using the HeLa 229 cell-culture model. Treating HeLa cells with chemical inhibitors of PI3K, Akt or Ras prior to bacterial infection inhibited GBS invasion but not attachment; treatment with 30 mu M LY294002 (PI3K inhibitor) reduced GBS invasion by 75%, 20 mu M L-6-hydroxymethyl-chiro-inositol 2-(R)-2-O-methyl-3-O-octadecylcarbonate (ICIO) (Akt inhibitor) reduced GBS invasion by 50%, and 10 mu M manumycin A (Ras inhibitor) inhibited GBS invasion by 90%. Genetic inactivation of the p85 alpha or p110 alpha PI3K subunits in HeLa cells also reduced GBS invasion by 55 and 30%, respectively. Western blot analysis revealed that phosphorylation of host-cell Akt and glycogen synthase kinase-3 (GSK-3) occurs in response to GBS infection, and that this is mediated upstream by PI3K. Infection of HeLa cells with GBS triggers pro-survival signalling and protects the HeLa cells from camptothecin-induced caspase-3 cleavage. The results from this investigation show that GIBS both requires and activates the PI3K/Akt host-cell signalling pathway during invasion of epithelial cells.
