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The Pseudomonas aeruginosa type III secretion system has an exotoxin S/T/Y independent pathogenic role during acute lung infection

Marlies Galle UGent, Shouguang Jin, Pieter Bogaert UGent, Mira Haegman UGent, Peter Vandenabeele UGent and Rudi Beyaert UGent (2012) PLOS ONE. 7(7).
abstract
The type III secretion system (T3SS) is a complex nanomachine of many pathogenic Gram-negative bacteria. It forms a proteinaceous channel that is inserted into the host eukaryotic cell membrane for injection of bacterial proteins that manipulate host cell signaling. However, few studies have focused on the effector-independent functions of the T3SS. Using a murine model of acute lung infection with Pseudomonas aeruginosa, an important human opportunistic pathogen, we compared the pathogenicity of mutant bacteria that lack all of the known effector toxins (Delta STY), with mutant bacteria that also lack the major translocator protein PopB (Delta STY/Delta PopB) and so cannot form a functional T3SS channel in the host cell membrane. Mortality was higher among mice challenged with Delta STY compared to mice challenged with Delta STY/Delta PopB mutant bacteria. In addition, mice infected with Delta STY showed decreased bacterial clearance from the lungs compared to those infected with Delta STY/Delta PopB. Infection was in both cases associated with substantial killing of lung infiltrating macrophages. However, macrophages from Delta STY-infected mice died by pro-inflammatory necrosis characterized by membrane permeabilization and caspase-1 mediated IL-1 beta production, whereas macrophages from Delta STY/Delta PopB infected mice died by apoptosis, which is characterized by annexin V positive staining of the cell membrane and caspase-3 activation. This was confirmed in macrophages infected in vitro. These results demonstrate a T3SS effector toxin independent role for the T3SS, in particular the T3SS translocator protein PopB, in the pathogenicity of P. aeruginosa during acute lung infection.
Please use this url to cite or link to this publication:
author
organization
year
type
journalArticle (original)
publication status
published
subject
keyword
IN-VITRO, YERSINIA-PSEUDOTUBERCULOSIS, PROTEIN SECRETION, VENTILATOR-ASSOCIATED PNEUMONIA, NEUTROPHIL APOPTOSIS, MACROPHAGE APOPTOSIS, NLRC4 INFLAMMASOME, EPITHELIAL-CELLS, TRANSLOCATION, EFFECTORS
journal title
PLOS ONE
PLoS One
volume
7
issue
7
article_number
e41547
pages
8 pages
Web of Science type
Article
Web of Science id
000306687700109
JCR category
MULTIDISCIPLINARY SCIENCES
JCR impact factor
3.73 (2012)
JCR rank
7/56 (2012)
JCR quartile
1 (2012)
ISSN
1932-6203
DOI
10.1371/journal.pone.0041547
project
Ghent researchers on unfolded proteins in inflammatory disease (GROUP-ID)
project
Ghent researchers on unfolded proteins in inflammatory disease (GROUP-ID)
language
English
UGent publication?
yes
classification
A1
copyright statement
I have retained and own the full copyright for this publication
id
2986467
handle
http://hdl.handle.net/1854/LU-2986467
date created
2012-09-13 13:38:27
date last changed
2014-05-12 11:01:07
@article{2986467,
  abstract     = {The type III secretion system (T3SS) is a complex nanomachine of many pathogenic Gram-negative bacteria. It forms a proteinaceous channel that is inserted into the host eukaryotic cell membrane for injection of bacterial proteins that manipulate host cell signaling. However, few studies have focused on the effector-independent functions of the T3SS. Using a murine model of acute lung infection with Pseudomonas aeruginosa, an important human opportunistic pathogen, we compared the pathogenicity of mutant bacteria that lack all of the known effector toxins (Delta STY), with mutant bacteria that also lack the major translocator protein PopB (Delta STY/Delta PopB) and so cannot form a functional T3SS channel in the host cell membrane. Mortality was higher among mice challenged with Delta STY compared to mice challenged with Delta STY/Delta PopB mutant bacteria. In addition, mice infected with Delta STY showed decreased bacterial clearance from the lungs compared to those infected with Delta STY/Delta PopB. Infection was in both cases associated with substantial killing of lung infiltrating macrophages. However, macrophages from Delta STY-infected mice died by pro-inflammatory necrosis characterized by membrane permeabilization and caspase-1 mediated IL-1 beta production, whereas macrophages from Delta STY/Delta PopB infected mice died by apoptosis, which is characterized by annexin V positive staining of the cell membrane and caspase-3 activation. This was confirmed in macrophages infected in vitro. These results demonstrate a T3SS effector toxin independent role for the T3SS, in particular the T3SS translocator protein PopB, in the pathogenicity of P. aeruginosa during acute lung infection.},
  articleno    = {e41547},
  author       = {Galle, Marlies and Jin, Shouguang and Bogaert, Pieter and Haegman, Mira and Vandenabeele, Peter and Beyaert, Rudi},
  issn         = {1932-6203},
  journal      = {PLOS ONE},
  keyword      = {IN-VITRO,YERSINIA-PSEUDOTUBERCULOSIS,PROTEIN SECRETION,VENTILATOR-ASSOCIATED PNEUMONIA,NEUTROPHIL APOPTOSIS,MACROPHAGE APOPTOSIS,NLRC4 INFLAMMASOME,EPITHELIAL-CELLS,TRANSLOCATION,EFFECTORS},
  language     = {eng},
  number       = {7},
  pages        = {8},
  title        = {The Pseudomonas aeruginosa type III secretion system has an exotoxin S/T/Y independent pathogenic role during acute lung infection},
  url          = {http://dx.doi.org/10.1371/journal.pone.0041547},
  volume       = {7},
  year         = {2012},
}

Chicago
Galle, Marlies, Shouguang Jin, Pieter Bogaert, Mira Haegman, Peter Vandenabeele, and Rudi Beyaert. 2012. “The Pseudomonas Aeruginosa Type III Secretion System Has an Exotoxin S/T/Y Independent Pathogenic Role During Acute Lung Infection.” Plos One 7 (7).
APA
Galle, Marlies, Jin, S., Bogaert, P., Haegman, M., Vandenabeele, P., & Beyaert, R. (2012). The Pseudomonas aeruginosa type III secretion system has an exotoxin S/T/Y independent pathogenic role during acute lung infection. PLOS ONE, 7(7).
Vancouver
1.
Galle M, Jin S, Bogaert P, Haegman M, Vandenabeele P, Beyaert R. The Pseudomonas aeruginosa type III secretion system has an exotoxin S/T/Y independent pathogenic role during acute lung infection. PLOS ONE. 2012;7(7).
MLA
Galle, Marlies, Shouguang Jin, Pieter Bogaert, et al. “The Pseudomonas Aeruginosa Type III Secretion System Has an Exotoxin S/T/Y Independent Pathogenic Role During Acute Lung Infection.” PLOS ONE 7.7 (2012): n. pag. Print.