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.
(Less)
- author
- Håkansson, Anders P
LU
; Bentley, Colette Cywes
; Shakhnovic, Elizabeth A
and Wessels, Michael R
- publishing date
- 2005-04-05
- 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
-
- pmid:15795386
- 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
- 2024-04-04 20:40:11
@article{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}},
keywords = {{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 = {{National Academy of Sciences}},
series = {{Proceedings of the National Academy of Sciences}},
title = {{Cytolysin-dependent evasion of lysosomal killing}},
url = {{http://dx.doi.org/10.1073/pnas.0408721102}},
doi = {{10.1073/pnas.0408721102}},
volume = {{102}},
year = {{2005}},
}