Document Detail


Invasion of HeLa cells by group B streptococcus requires the phosphoinositide-3-kinase signalling pathway and modulates phosphorylation of host-cell Akt and glycogen synthase kinase-3.
MedLine Citation:
PMID:  18048937     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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 microM LY294002 (PI3K inhibitor) reduced GBS invasion by 75%, 20 microM L-6-hydroxymethyl-chiro-inositol 2-(R)-2-O-methyl-3-O-octadecylcarbonate (ICIO) (Akt inhibitor) reduced GBS invasion by 50%, and 10 microM manumycin A (Ras inhibitor) inhibited GBS invasion by 90%. Genetic inactivation of the p85alpha or p110alpha 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 GBS both requires and activates the PI3K/Akt host-cell signalling pathway during invasion of epithelial cells.
Authors:
Carey-Ann D Burnham; Sandra E Shokoples; Gregory J Tyrrell
Related Documents :
6541657 - Microfilament organization and total actin content are decreased in hybrids derived fro...
22445757 - The p53 inhibitor, pifithrin-α, suppresses self-renewal of embryonic stem cells.
18948597 - Kinase requirements in human cells: iv. differential kinase requirements in cervical an...
10635337 - Effect of various concentrations of acyclovir on cell survival and micronuclei inductio...
21950797 - The efficiency of the co(2) -concentrating mechanism during single-cell c(4) photosynth...
22367497 - Zinc induces caspase-dependent mitochondrial pathway of the programmed cell death in ha...
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Microbiology (Reading, England)     Volume:  153     ISSN:  1350-0872     ISO Abbreviation:  Microbiology (Reading, Engl.)     Publication Date:  2007 Dec 
Date Detail:
Created Date:  2007-11-30     Completed Date:  2008-02-19     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  9430468     Medline TA:  Microbiology     Country:  England    
Other Details:
Languages:  eng     Pagination:  4240-52     Citation Subset:  IM    
Affiliation:
The Department of Laboratory Medicine and Pathology, The University of Alberta, Edmonton, AB, Canada.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
1-Phosphatidylinositol 3-Kinase / metabolism*
Bacterial Adhesion
Epithelial Cells / microbiology*
Gene Expression Regulation*
Glycogen Synthase Kinases / genetics,  metabolism*
Hela Cells / microbiology
Humans
Phosphorylation
Proto-Oncogene Proteins c-akt / genetics,  metabolism*
Signal Transduction*
Streptococcus agalactiae / pathogenicity*
Chemical
Reg. No./Substance:
EC 2.7.1.137/1-Phosphatidylinositol 3-Kinase; EC 2.7.11.-/Glycogen Synthase Kinases; EC 2.7.11.1/Proto-Oncogene Proteins c-akt

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  The stringent response of Bacillus anthracis contributes to sporulation but not to virulence.
Next Document:  Characterization of the NAD-glycohydrolase in streptococcal strains.