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.
(Less)
- author
- Cywes Bentley, Colette
; Hakansson, Anders
LU
; Christianson, Jennifer
and Wessels, Michael R
- publishing date
- 2005-07
- 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
-
- pmid:15953027
- 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
- 2024-04-19 01:31:02
@article{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}},
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}},
language = {{eng}},
number = {{7}},
pages = {{55--945}},
publisher = {{Wiley-Blackwell}},
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}},
doi = {{10.1111/j.1462-5822.2005.00525.x}},
volume = {{7}},
year = {{2005}},
}