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Cell Host Microbe. 2013 Dec 11;14(6):675-82. doi: 10.1016/j.chom.2013.11.003.

The globally disseminated M1T1 clone of group A Streptococcus evades autophagy for intracellular replication.

Author information

  • 1Australian Infectious Diseases Research Centre, The University of Queensland, Queensland, St Lucia, QLD 4072, Australia; School of Chemistry and Molecular Biosciences, The University of Queensland, Queensland, St Lucia, QLD 4072, Australia.
  • 2Institute for Molecular Bioscience, The University of Queensland, Queensland, St Lucia, QLD 4072, Australia.
  • 3Department of Pediatrics and Skaggs School of Pharmacy & Pharmaceutical Sciences, University of California, San Diego, La Jolla, CA 92093, USA.
  • 4Australian Infectious Diseases Research Centre, The University of Queensland, Queensland, St Lucia, QLD 4072, Australia; School of Chemistry and Molecular Biosciences, The University of Queensland, Queensland, St Lucia, QLD 4072, Australia; Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, UK.
  • 5Australian Infectious Diseases Research Centre, The University of Queensland, Queensland, St Lucia, QLD 4072, Australia; Institute for Molecular Bioscience, The University of Queensland, Queensland, St Lucia, QLD 4072, Australia.
  • 6Australian Infectious Diseases Research Centre, The University of Queensland, Queensland, St Lucia, QLD 4072, Australia; School of Chemistry and Molecular Biosciences, The University of Queensland, Queensland, St Lucia, QLD 4072, Australia. Electronic address: mark.walker@uq.edu.au.

Abstract

Autophagy is reported to be an important innate immune defense against the intracellular bacterial pathogen Group A Streptococcus (GAS). However, the GAS strains examined to date belong to serotypes infrequently associated with human disease. We find that the globally disseminated serotype M1T1 clone of GAS can evade autophagy and replicate efficiently in the cytosol of infected cells. Cytosolic M1T1 GAS (strain 5448), but not M6 GAS (strain JRS4), avoids ubiquitylation and recognition by the host autophagy marker LC3 and ubiquitin-LC3 adaptor proteins NDP52, p62, and NBR1. Expression of SpeB, a streptococcal cysteine protease, is critical for this process, as an isogenic M1T1 ΔspeB mutant is targeted to autophagy and attenuated for intracellular replication. SpeB degrades p62, NDP52, and NBR1 in vitro and within the host cell cytosol. These results uncover a proteolytic mechanism utilized by GAS to escape the host autophagy pathway that may underpin the success of the M1T1 clone.

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PMID:
24331465
PMCID:
PMC3918495
DOI:
10.1016/j.chom.2013.11.003
[PubMed - indexed for MEDLINE]
Free PMC Article
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