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Extracellular group A Streptococcus induces keratinocyte apoptosis by dysregulating calcium signalling

Cywes Bentley, Colette; Hakansson, Anders LU ; Christianson, Jennifer and Wessels, Michael R (2005) In Cellular Microbiology 7(7). p.55-945
Abstract

Group A Streptococcus (GAS) colonizes the oropharynx and damaged skin. To cause local infection or severe invasive syndromes the bacteria must gain access into deeper tissues. Host cell death may facilitate this process. GAS internalization has been identified to induce apoptosis. We now report an alternate mechanism of GAS-mediated apoptosis of primary human keratinocytes, initiated by extracellular GAS and involving dysregulation of intracellular calcium to produce endoplasmic reticulum stress. Two bacterial virulence factors are required for effective induction of apoptosis by extracellular GAS: (i) hyaluronic acid capsule that inhibits bacterial internalization and (ii) secreted cytolysin, streptolysin O (SLO), that forms... (More)

Group A Streptococcus (GAS) colonizes the oropharynx and damaged skin. To cause local infection or severe invasive syndromes the bacteria must gain access into deeper tissues. Host cell death may facilitate this process. GAS internalization has been identified to induce apoptosis. We now report an alternate mechanism of GAS-mediated apoptosis of primary human keratinocytes, initiated by extracellular GAS and involving dysregulation of intracellular calcium to produce endoplasmic reticulum stress. Two bacterial virulence factors are required for effective induction of apoptosis by extracellular GAS: (i) hyaluronic acid capsule that inhibits bacterial internalization and (ii) secreted cytolysin, streptolysin O (SLO), that forms transmembrane pores that permit extracellular calcium influx into the cytosol. Induction of keratinocyte apoptosis by wild-type GAS was accompanied by cell detachment and loss of epithelial integrity, a phenomenon not observed with GAS deficient in capsule or SLO. We propose that cell signalling initiated by extracellular GAS compromises the epithelial barrier by inducing premature keratinocyte differentiation and apoptosis, thereby facilitating GAS invasion of deeper tissues.

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author
publishing date
type
Contribution to journal
publication status
published
keywords
Antigens, CD44, Apoptosis, Bacterial Capsules, Bacterial Proteins, Boron Compounds, Calcium, Calcium Signaling, Cell Line, Cytoplasm, DNA Fragmentation, Endoplasmic Reticulum, Humans, In Situ Nick-End Labeling, Keratinocytes, Mitochondria, Permeability, Streptococcus pyogenes, Streptolysins, Vacuoles
in
Cellular Microbiology
volume
7
issue
7
pages
11 pages
publisher
Wiley-Blackwell
external identifiers
  • Scopus:21344467496
ISSN
1462-5814
DOI
10.1111/j.1462-5822.2005.00525.x
language
English
LU publication?
no
id
1a63518f-0f41-492a-82b6-f81d4116d3a7
date added to LUP
2016-05-21 13:53:14
date last changed
2016-11-01 08:40:17
@misc{1a63518f-0f41-492a-82b6-f81d4116d3a7,
  abstract     = {<p>Group A Streptococcus (GAS) colonizes the oropharynx and damaged skin. To cause local infection or severe invasive syndromes the bacteria must gain access into deeper tissues. Host cell death may facilitate this process. GAS internalization has been identified to induce apoptosis. We now report an alternate mechanism of GAS-mediated apoptosis of primary human keratinocytes, initiated by extracellular GAS and involving dysregulation of intracellular calcium to produce endoplasmic reticulum stress. Two bacterial virulence factors are required for effective induction of apoptosis by extracellular GAS: (i) hyaluronic acid capsule that inhibits bacterial internalization and (ii) secreted cytolysin, streptolysin O (SLO), that forms transmembrane pores that permit extracellular calcium influx into the cytosol. Induction of keratinocyte apoptosis by wild-type GAS was accompanied by cell detachment and loss of epithelial integrity, a phenomenon not observed with GAS deficient in capsule or SLO. We propose that cell signalling initiated by extracellular GAS compromises the epithelial barrier by inducing premature keratinocyte differentiation and apoptosis, thereby facilitating GAS invasion of deeper tissues.</p>},
  author       = {Cywes Bentley, Colette and Hakansson, Anders and Christianson, Jennifer and Wessels, Michael R},
  issn         = {1462-5814},
  keyword      = {Antigens, CD44,Apoptosis,Bacterial Capsules,Bacterial Proteins,Boron Compounds,Calcium,Calcium Signaling,Cell Line,Cytoplasm,DNA Fragmentation,Endoplasmic Reticulum,Humans,In Situ Nick-End Labeling,Keratinocytes,Mitochondria,Permeability,Streptococcus pyogenes,Streptolysins,Vacuoles},
  language     = {eng},
  number       = {7},
  pages        = {55--945},
  publisher    = {ARRAY(0xa0d2830)},
  series       = {Cellular Microbiology},
  title        = {Extracellular group A Streptococcus induces keratinocyte apoptosis by dysregulating calcium signalling},
  url          = {http://dx.doi.org/10.1111/j.1462-5822.2005.00525.x},
  volume       = {7},
  year         = {2005},
}