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

Barnett, Timothy C., Liebl, David, Seymour, Lisa M., Gillen, Christine M., Lim, Jin Yan, LaRock, Christopher N., Davies, Mark R., Schulz, Benjamin L., Nizet, Victor, Teasdale, Rohan D. and Walker, Mark J. (2013) The globally disseminated M1T1 clone of Group A Streptococcus evades autophagy for intracellular replication. Cell Host and Microbe, 14 6: 675-682. doi:10.1016/j.chom.2013.11.003


Author Barnett, Timothy C.
Liebl, David
Seymour, Lisa M.
Gillen, Christine M.
Lim, Jin Yan
LaRock, Christopher N.
Davies, Mark R.
Schulz, Benjamin L.
Nizet, Victor
Teasdale, Rohan D.
Walker, Mark J.
Title The globally disseminated M1T1 clone of Group A Streptococcus evades autophagy for intracellular replication
Formatted title
The globally disseminated M1T1 clone of Group A Streptococcus evades autophagy for intracellular replication
Journal name Cell Host and Microbe   Check publisher's open access policy
ISSN 1931-3128
1934-6069
Publication date 2013-12-11
Sub-type Article (original research)
DOI 10.1016/j.chom.2013.11.003
Volume 14
Issue 6
Start page 675
End page 682
Total pages 8
Place of publication Cambridge, MA, United States
Publisher Cell Press
Collection year 2014
Language eng
Formatted 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.
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2014 Collection
School of Chemistry and Molecular Biosciences
Institute for Molecular Bioscience - Publications
 
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Citation counts: TR Web of Science Citation Count  Cited 30 times in Thomson Reuters Web of Science Article | Citations
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Created: Tue, 17 Dec 2013, 20:38:57 EST by Susan Allen on behalf of Institute for Molecular Bioscience