Bacillus anthracis spore entry into epithelial cells is an actin-dependent process requiring c-Src and PI3K.

PloS One
Qiong XueYi Xu

Abstract

Dissemination of Bacillus anthracis from the respiratory mucosa is a critical step in the establishment of inhalational anthrax. Recent in vitro and in vivo studies indicated that this organism was able to penetrate the lung epithelium by directly entering into epithelial cells of the lung; however the molecular details of B. anthracis breaching the epithelium were lacking. Here, using a combination of pharmacological inhibitors, dominant negative mutants, and colocalization experiments, we demonstrated that internalization of spores by epithelial cells was actin-dependent and was mediated by the Rho-family GTPase Cdc42 but not RhoA or Rac1. Phosphatidylinositol 3-kinase (PI3K) activity was also required as indicated by the inhibitory effects of PI3K inhibitors, wortmannin and LY294002, and a PI3K dominant negative (DN) mutant Deltap85alpha. In addition, spore entry into epithelial cells (but not into macrophages) required the activity of Src as indicated by the inhibitory effect of Src family kinase (SFK) inhibitors, PP2 and SU6656, and specific siRNA knockdown of Src. Enrichment of PI3K and F-actin around spore attachment sites was observed and was significantly reduced by treatment with SFK and PI3K inhibitors, respectively....Continue Reading

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Citations

Apr 21, 2012·Journal of Applied Microbiology·M D BensmanB W Gutting
Jun 12, 2013·PloS One·Sarah A Jenkins, Yi Xu
Oct 30, 2015·Microbiology and Molecular Biology Reviews : MMBR·George C Stewart
Mar 24, 2012·The Journal of Immunology : Official Journal of the American Association of Immunologists·Chunfang GuYi Xu

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Methods Mentioned

BETA
GTPase
transfection
GTPases
fluorescence microscopy
nucleotide exchange
X-ray

Software Mentioned

GraphPad Prism
LSM

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