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V-ATPase-mediated phagosomal acidification is impaired by Streptococcus pyogenes through Mga-regulated surface proteins.

Nordenfelt, Pontus LU ; Grinstein, Sergio; Björck, Lars LU and Tapper, Hans LU (2012) In Microbes and Infection
Abstract
Streptococcus pyogenes, a significant bacterial pathogen in humans, interferes with the membrane traffic of human neutrophils and survives following phagocytosis. The mechanism(s) behind this property is not known, but in contrast to wild-type bacteria, mutant bacteria lacking virulence factors regulated by the transcriptional regulator Mga, are phagocytosed and killed. In the present work we investigated whether differences in phagosomal acidification may contribute to this difference. Phagosomal pH in neutrophil-differentiated HL-60 cells was studied by fluorescence ratio imaging, and phagosomes containing wild-type S. pyogenes bacteria of the M1 serotype exhibited little or no acidification, whereas Mga mutant bacteria were found in... (More)
Streptococcus pyogenes, a significant bacterial pathogen in humans, interferes with the membrane traffic of human neutrophils and survives following phagocytosis. The mechanism(s) behind this property is not known, but in contrast to wild-type bacteria, mutant bacteria lacking virulence factors regulated by the transcriptional regulator Mga, are phagocytosed and killed. In the present work we investigated whether differences in phagosomal acidification may contribute to this difference. Phagosomal pH in neutrophil-differentiated HL-60 cells was studied by fluorescence ratio imaging, and phagosomes containing wild-type S. pyogenes bacteria of the M1 serotype exhibited little or no acidification, whereas Mga mutant bacteria were found in more acidic phagosomes. With phagosomes containing these bacteria, proton delivery was inhibited by adding folimycin, a vacuolar-type adenosine triphosphatase (V-ATPase) inhibitor. This inhibitor had no effect on phagosomes containing wild-type bacteria, indicating either inactivation or removal of V-ATPases by the bacteria. Analysis of isolated bacteria-containing phagosomes confirmed the latter scenario and showed a more efficient delivery of V-ATPases to phagosomes containing Mga mutant bacteria. The results demonstrate that V-ATPase-mediated phagosomal proton delivery is reduced during phagocytosis of wild-type S. pyogenes, leading to impaired acidification, and that surface proteins of the mga regulon are responsible for this effect. (Less)
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Contribution to journal
publication status
published
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Microbes and Infection
publisher
Elsevier
external identifiers
  • wos:000312418700011
  • pmid:22981599
  • scopus:84870235252
ISSN
1769-714X
DOI
10.1016/j.micinf.2012.08.005
language
English
LU publication?
yes
id
25f8dc37-29cd-40d0-84e7-79355b68d020 (old id 3123920)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/22981599?dopt=Abstract
date added to LUP
2012-10-02 14:49:24
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2017-11-05 04:42:06
@article{25f8dc37-29cd-40d0-84e7-79355b68d020,
  abstract     = {Streptococcus pyogenes, a significant bacterial pathogen in humans, interferes with the membrane traffic of human neutrophils and survives following phagocytosis. The mechanism(s) behind this property is not known, but in contrast to wild-type bacteria, mutant bacteria lacking virulence factors regulated by the transcriptional regulator Mga, are phagocytosed and killed. In the present work we investigated whether differences in phagosomal acidification may contribute to this difference. Phagosomal pH in neutrophil-differentiated HL-60 cells was studied by fluorescence ratio imaging, and phagosomes containing wild-type S. pyogenes bacteria of the M1 serotype exhibited little or no acidification, whereas Mga mutant bacteria were found in more acidic phagosomes. With phagosomes containing these bacteria, proton delivery was inhibited by adding folimycin, a vacuolar-type adenosine triphosphatase (V-ATPase) inhibitor. This inhibitor had no effect on phagosomes containing wild-type bacteria, indicating either inactivation or removal of V-ATPases by the bacteria. Analysis of isolated bacteria-containing phagosomes confirmed the latter scenario and showed a more efficient delivery of V-ATPases to phagosomes containing Mga mutant bacteria. The results demonstrate that V-ATPase-mediated phagosomal proton delivery is reduced during phagocytosis of wild-type S. pyogenes, leading to impaired acidification, and that surface proteins of the mga regulon are responsible for this effect.},
  author       = {Nordenfelt, Pontus and Grinstein, Sergio and Björck, Lars and Tapper, Hans},
  issn         = {1769-714X},
  language     = {eng},
  month        = {08},
  publisher    = {Elsevier},
  series       = {Microbes and Infection},
  title        = {V-ATPase-mediated phagosomal acidification is impaired by Streptococcus pyogenes through Mga-regulated surface proteins.},
  url          = {http://dx.doi.org/10.1016/j.micinf.2012.08.005},
  year         = {2012},
}