Advanced

Streptolysin O inhibits clathrin-dependent internalization of group A Streptococcus

Logsdon, Lauren K; Håkansson, Anders P LU ; Wessels, Michael R and Cortés, Guadalupe (2011) In mBio 2(1). p.10-00332
Abstract

Group A Streptococcus (GAS) can be internalized by epithelial cells, including keratinocytes from human skin or pharyngeal epithelium. Internalization of GAS by epithelial cells has been postulated both to play a role in host defense and to provide a sanctuary site for GAS survival. The cholesterol-binding cytolysin streptolysin O (SLO) appears to enhance virulence in part by inhibiting GAS internalization by human keratinocytes and by disrupting the lysosomal degradation of internalized GAS. We now report that low-level production of SLO by an inducible expression system reduced GAS internalization by keratinocytes. Induced SLO expression also prevented lysosomal colocalization with intracellular bacteria and acidification of... (More)

Group A Streptococcus (GAS) can be internalized by epithelial cells, including keratinocytes from human skin or pharyngeal epithelium. Internalization of GAS by epithelial cells has been postulated both to play a role in host defense and to provide a sanctuary site for GAS survival. The cholesterol-binding cytolysin streptolysin O (SLO) appears to enhance virulence in part by inhibiting GAS internalization by human keratinocytes and by disrupting the lysosomal degradation of internalized GAS. We now report that low-level production of SLO by an inducible expression system reduced GAS internalization by keratinocytes. Induced SLO expression also prevented lysosomal colocalization with intracellular bacteria and acidification of GAS-containing vacuoles. Exogenous recombinant SLO mimicked the inhibitory effect of SLO secretion on GAS entry but not that on colocalization with the lysosomal marker LAMP-1, implying that disruption of lysosomal degradation requires intracellular secretion of SLO. The internalization of SLO-negative GAS was blocked by the depletion of host cell cholesterol and by the inhibition or knocking down of the expression of clathrin or dynamin. SLO also inhibited the cellular uptake of other cargos that are internalized by clathrin-mediated uptake or by macropinocytosis. We conclude that SLO interferes with the internalization of GAS through local perturbation of the keratinocyte cell membrane and disruption of a clathrin-dependent uptake pathway.

(Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Bacterial Proteins, Cell Line, Clathrin, Down-Regulation, Dynamins, Gene Expression Regulation, Bacterial, Humans, Keratinocytes, Streptococcal Infections, Streptococcus pyogenes, Streptolysins
in
mBio
volume
2
issue
1
pages
10 - 00332
publisher
American Society for Microbiology
external identifiers
  • scopus:79955082658
ISSN
2161-2129
DOI
10.1128/mBio.00332-10
language
English
LU publication?
yes
id
7922d620-9788-4f49-9450-e6d1ca0c9bcf
date added to LUP
2016-05-21 10:51:05
date last changed
2017-06-25 04:51:34
@article{7922d620-9788-4f49-9450-e6d1ca0c9bcf,
  abstract     = {<p>Group A Streptococcus (GAS) can be internalized by epithelial cells, including keratinocytes from human skin or pharyngeal epithelium. Internalization of GAS by epithelial cells has been postulated both to play a role in host defense and to provide a sanctuary site for GAS survival. The cholesterol-binding cytolysin streptolysin O (SLO) appears to enhance virulence in part by inhibiting GAS internalization by human keratinocytes and by disrupting the lysosomal degradation of internalized GAS. We now report that low-level production of SLO by an inducible expression system reduced GAS internalization by keratinocytes. Induced SLO expression also prevented lysosomal colocalization with intracellular bacteria and acidification of GAS-containing vacuoles. Exogenous recombinant SLO mimicked the inhibitory effect of SLO secretion on GAS entry but not that on colocalization with the lysosomal marker LAMP-1, implying that disruption of lysosomal degradation requires intracellular secretion of SLO. The internalization of SLO-negative GAS was blocked by the depletion of host cell cholesterol and by the inhibition or knocking down of the expression of clathrin or dynamin. SLO also inhibited the cellular uptake of other cargos that are internalized by clathrin-mediated uptake or by macropinocytosis. We conclude that SLO interferes with the internalization of GAS through local perturbation of the keratinocyte cell membrane and disruption of a clathrin-dependent uptake pathway.</p>},
  author       = {Logsdon, Lauren K and Håkansson, Anders P and Wessels, Michael R and Cortés, Guadalupe},
  issn         = {2161-2129},
  keyword      = {Bacterial Proteins,Cell Line,Clathrin,Down-Regulation,Dynamins,Gene Expression Regulation, Bacterial,Humans,Keratinocytes,Streptococcal Infections,Streptococcus pyogenes,Streptolysins},
  language     = {eng},
  number       = {1},
  pages        = {10--00332},
  publisher    = {American Society for Microbiology},
  series       = {mBio},
  title        = {Streptolysin O inhibits clathrin-dependent internalization of group A Streptococcus},
  url          = {http://dx.doi.org/10.1128/mBio.00332-10},
  volume       = {2},
  year         = {2011},
}