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Cytolysin-dependent evasion of lysosomal killing

Håkansson, Anders P LU ; Bentley, Colette Cywes; Shakhnovic, Elizabeth A and Wessels, Michael R (2005) In Proceedings of the National Academy of Sciences 102(14). p.5192-5197
Abstract

Local host defenses limit proliferation and systemic spread of pathogenic bacteria from sites of mucosal colonization. For pathogens such as streptococci that fail to grow intracellularly, internalization and killing by epithelial cells contribute to the control of bacterial growth and dissemination. Here, we show that group A Streptococcus (GAS), the agent of streptococcal sore throat and invasive soft tissue infections, evades internalization and intracellular killing by pharyngeal epithelial cells. Production of the cholesterol-binding cytotoxin streptolysin O (SLO) prevented internalization of GAS into lysosomes. In striking contrast, GAS rendered defective in production of SLO were internalized directly or rapidly transported into... (More)

Local host defenses limit proliferation and systemic spread of pathogenic bacteria from sites of mucosal colonization. For pathogens such as streptococci that fail to grow intracellularly, internalization and killing by epithelial cells contribute to the control of bacterial growth and dissemination. Here, we show that group A Streptococcus (GAS), the agent of streptococcal sore throat and invasive soft tissue infections, evades internalization and intracellular killing by pharyngeal epithelial cells. Production of the cholesterol-binding cytotoxin streptolysin O (SLO) prevented internalization of GAS into lysosomes. In striking contrast, GAS rendered defective in production of SLO were internalized directly or rapidly transported into lysosomes, where they were killed by a pH-dependent mechanism. Because SLO is the prototype of cholesterol-dependent cytolysins produced by many Gram-positive bacteria, cytolysin-mediated evasion of lysosomal killing may be a general mechanism to protect such pathogens from clearance by host epithelial cells.

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author
publishing date
type
Contribution to journal
publication status
published
keywords
Bacterial Proteins, Cells, Cultured, Exocytosis, Genes, Bacterial, Humans, Hydrogen-Ion Concentration, Immunity, Mucosal, Keratinocytes, Lysosomes, Mutation, Oropharynx, Streptococcus pyogenes, Streptolysins, Virulence
in
Proceedings of the National Academy of Sciences
volume
102
issue
14
pages
6 pages
publisher
National Academy of Sciences
external identifiers
  • Scopus:17044439490
ISSN
0027-8424
DOI
10.1073/pnas.0408721102
language
English
LU publication?
no
id
cb6fe04b-d2f8-45fb-87d7-8e67e2218d8d
date added to LUP
2016-05-21 13:53:56
date last changed
2016-10-13 05:09:17
@misc{cb6fe04b-d2f8-45fb-87d7-8e67e2218d8d,
  abstract     = {<p>Local host defenses limit proliferation and systemic spread of pathogenic bacteria from sites of mucosal colonization. For pathogens such as streptococci that fail to grow intracellularly, internalization and killing by epithelial cells contribute to the control of bacterial growth and dissemination. Here, we show that group A Streptococcus (GAS), the agent of streptococcal sore throat and invasive soft tissue infections, evades internalization and intracellular killing by pharyngeal epithelial cells. Production of the cholesterol-binding cytotoxin streptolysin O (SLO) prevented internalization of GAS into lysosomes. In striking contrast, GAS rendered defective in production of SLO were internalized directly or rapidly transported into lysosomes, where they were killed by a pH-dependent mechanism. Because SLO is the prototype of cholesterol-dependent cytolysins produced by many Gram-positive bacteria, cytolysin-mediated evasion of lysosomal killing may be a general mechanism to protect such pathogens from clearance by host epithelial cells.</p>},
  author       = {Håkansson, Anders P and Bentley, Colette Cywes and Shakhnovic, Elizabeth A and Wessels, Michael R},
  issn         = {0027-8424},
  keyword      = {Bacterial Proteins,Cells, Cultured,Exocytosis,Genes, Bacterial,Humans,Hydrogen-Ion Concentration,Immunity, Mucosal,Keratinocytes,Lysosomes,Mutation,Oropharynx,Streptococcus pyogenes,Streptolysins,Virulence},
  language     = {eng},
  month        = {04},
  number       = {14},
  pages        = {5192--5197},
  publisher    = {ARRAY(0xa96c2a0)},
  series       = {Proceedings of the National Academy of Sciences},
  title        = {Cytolysin-dependent evasion of lysosomal killing},
  url          = {http://dx.doi.org/10.1073/pnas.0408721102},
  volume       = {102},
  year         = {2005},
}