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M1 Protein-Dependent Intracellular Trafficking Promotes Persistence and Replication of Streptococcus pyogenes in Macrophages

Hertzen, Erika; Johansson, Linda; Wallin, Robert; Schmidt, Heike; Kroll, Mirko; Rehn, Anders P.; Kotb, Malak; Mörgelin, Matthias LU and Norrby-Teglund, Anna (2010) In Journal of Innate Immunity 2(6). p.534-545
Abstract
Streptococcus pyogenes is an important human pathogen that causes a variety of diseases including life-threatening invasive diseases, such as toxic shock and deep tissue infections. Although S. pyogenes are classically considered extracellular pathogens, a clinical significance of an intracellular source has been emphasized. In patients with deep tissue infections, an intracellular reservoir of S. pyogenes within macrophages was shown to contribute to prolonged bacterial persistence. Here we demonstrate that intracellular survival of S. pyogenes in macrophages is associated with an M1 protein-dependent intracellular trafficking in the phagosomal-lysosomal pathway, which results in impaired fusion with lysosomes. The phagocytic vacuoles... (More)
Streptococcus pyogenes is an important human pathogen that causes a variety of diseases including life-threatening invasive diseases, such as toxic shock and deep tissue infections. Although S. pyogenes are classically considered extracellular pathogens, a clinical significance of an intracellular source has been emphasized. In patients with deep tissue infections, an intracellular reservoir of S. pyogenes within macrophages was shown to contribute to prolonged bacterial persistence. Here we demonstrate that intracellular survival of S. pyogenes in macrophages is associated with an M1 protein-dependent intracellular trafficking in the phagosomal-lysosomal pathway, which results in impaired fusion with lysosomes. The phagocytic vacuoles harbouring M1 protein-expressing bacteria not only served as a safe haven for the bacteria, but also as a replicating niche. An M1 protein-dependent modulation of macrophages was further supported by differences in NF-kappa B signalling between cells infected with either the wild-type or M1 protein-deficient strains, thereby indicating a suppressed inflammatory response when M1 protein was involved. Evidence of egress of bacteria out of their host cell and subsequent re-infection of new cells emphasize the importance of intracellular bacteria as a reservoir for dissemination of infection and continued tissue injury. Copyright (C) 2010 S. Karger AG, Basel (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
protein, Host-pathogen interaction, M, Macrophage, Streptococcus pyogenes, Intracellular persistence
in
Journal of Innate Immunity
volume
2
issue
6
pages
534 - 545
publisher
Karger
external identifiers
  • wos:000283333700004
  • scopus:77958177658
ISSN
1662-811X
DOI
10.1159/000317635
language
English
LU publication?
yes
id
1642062f-0675-4b53-b4ea-73a34ebe739e (old id 1720792)
date added to LUP
2010-12-03 14:15:43
date last changed
2018-07-01 03:15:00
@article{1642062f-0675-4b53-b4ea-73a34ebe739e,
  abstract     = {Streptococcus pyogenes is an important human pathogen that causes a variety of diseases including life-threatening invasive diseases, such as toxic shock and deep tissue infections. Although S. pyogenes are classically considered extracellular pathogens, a clinical significance of an intracellular source has been emphasized. In patients with deep tissue infections, an intracellular reservoir of S. pyogenes within macrophages was shown to contribute to prolonged bacterial persistence. Here we demonstrate that intracellular survival of S. pyogenes in macrophages is associated with an M1 protein-dependent intracellular trafficking in the phagosomal-lysosomal pathway, which results in impaired fusion with lysosomes. The phagocytic vacuoles harbouring M1 protein-expressing bacteria not only served as a safe haven for the bacteria, but also as a replicating niche. An M1 protein-dependent modulation of macrophages was further supported by differences in NF-kappa B signalling between cells infected with either the wild-type or M1 protein-deficient strains, thereby indicating a suppressed inflammatory response when M1 protein was involved. Evidence of egress of bacteria out of their host cell and subsequent re-infection of new cells emphasize the importance of intracellular bacteria as a reservoir for dissemination of infection and continued tissue injury. Copyright (C) 2010 S. Karger AG, Basel},
  author       = {Hertzen, Erika and Johansson, Linda and Wallin, Robert and Schmidt, Heike and Kroll, Mirko and Rehn, Anders P. and Kotb, Malak and Mörgelin, Matthias and Norrby-Teglund, Anna},
  issn         = {1662-811X},
  keyword      = {protein,Host-pathogen interaction,M,Macrophage,Streptococcus pyogenes,Intracellular persistence},
  language     = {eng},
  number       = {6},
  pages        = {534--545},
  publisher    = {Karger},
  series       = {Journal of Innate Immunity},
  title        = {M1 Protein-Dependent Intracellular Trafficking Promotes Persistence and Replication of Streptococcus pyogenes in Macrophages},
  url          = {http://dx.doi.org/10.1159/000317635},
  volume       = {2},
  year         = {2010},
}