Journal article
The globally disseminated M1T1 clone of group a streptococcus evades autophagy for intracellular replication
TC Barnett, D Liebl, LM Seymour, CM Gillen, JY Lim, CN Larock, MR Davies, BL Schulz, V Nizet, RD Teasdale, MJ Walker
Cell Host and Microbe | CELL PRESS | Published : 2013
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 i..
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Awarded by National Institutes of Health
Funding Acknowledgements
Microscopy was carried out at the Australian Cancer Research Foundation (ACRF) Cancer Biology Imaging Facility at the Institute for Molecular Bioscience. Electron microscopy was carried out at The Centre for Microscopy and Microanalysis (the Queensland Node of the Australian Microscopy and Microanalysis Research Facility). We thank Ericka Anderson for additional experimental assistance. This work was supported by funding from the National Health and Medical Research Council (NHMRC) of Australia (1041294, 631386, 635250, 565526, 1041929, and 606788) and the National Institutes of Health (NIH) of the United States of America (AI077780, AI057153, and AR052728).