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

Barnett, Timothy C. and Liebl, David and Seymour, Lisa M. and Gillen, Christine M. and Yan Lim, Jin and LaRock, Christopher N. and Davies, Mark R. and Schulz, Benjamin L. and Nizet, Victor and 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. ISSN 1931-3128

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.


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Item Type: Article (Commonwealth Reporting Category C)
Refereed: Yes
Item Status: Live Archive
Additional Information: © 2013 Elsevier Inc. Published version deposited but restricted in accordance with the copyright policy of the publisher.
Faculty / Department / School: Historic - Faculty of Health, Engineering and Sciences - School of Health, Nursing and Midwifery
Date Deposited: 16 Apr 2014 21:44
Last Modified: 28 Sep 2016 04:54
Uncontrolled Keywords: autophagy; Group A Streptococcus (GAS); adaptor protein; cysteine proteinase; NBR1 protein; NDP52 protein; protein p62; speb protein; cysteine proteinase
Fields of Research : 11 Medical and Health Sciences > 1108 Medical Microbiology > 110801 Medical Bacteriology
06 Biological Sciences > 0605 Microbiology > 060502 Infectious Agents
Socio-Economic Objective: C Society > 92 Health > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920109 Infectious Diseases
Identification Number or DOI: 10.1016/j.chom.2013.11.003
URI: http://eprints.usq.edu.au/id/eprint/25091

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