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

Article

Barnett, Timothy C., Liebl, David, Seymour, Lisa M., Gillen, Christine M., Yan Lim, Jin, 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), pp. 675-682. https://doi.org/10.1016/j.chom.2013.11.003
Article Title

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

ERA Journal ID2525
Article CategoryArticle
AuthorsBarnett, Timothy C. (Author), Liebl, David (Author), Seymour, Lisa M. (Author), Gillen, Christine M. (Author), Yan Lim, Jin (Author), LaRock, Christopher N. (Author), Davies, Mark R. (Author), Schulz, Benjamin L. (Author), Nizet, Victor (Author), Teasdale, Rohan D. (Author) and Walker, Mark J. (Author)
Journal TitleCell Host and Microbe
Journal Citation14 (6), pp. 675-682
Number of Pages8
Year2013
Place of PublicationCambridge, MA. United States
ISSN1931-3128
1934-6069
Digital Object Identifier (DOI)https://doi.org/10.1016/j.chom.2013.11.003
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 DspeB 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.

Keywordsautophagy; Group A Streptococcus (GAS); adaptor protein; cysteine proteinase; NBR1 protein; NDP52 protein; protein p62; speb protein; cysteine proteinase
ANZSRC Field of Research 2020320701. Medical bacteriology
310702. Infectious agents
Public Notes

© 2013 Elsevier Inc. Published version deposited but restricted in accordance with the copyright policy of the publisher.

Byline AffiliationsUniversity of Queensland
University of California, United States
Institution of OriginUniversity of Southern Queensland
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