The Globally Disseminated M1T1 Clone of Group A Streptococcus Evades Autophagy for Intracellular Replication

Timothy C. Barnett, David Liebl, Lisa M. Seymour, Christine M. Gillen, Jin Yan Lim, Christopher N. LaRock, Mark R. Davies, Benjamin L. Schulz, Victor Nizet, Rohan D. Teasdale, and Mark J. Walker. Cell Host Microbe. 2013 Dec 11;14(6):675-82.

Speaker: Dong Sheng Lin(林東昇)                              Time: 14:00~15:00, Feb. 26, 2014

Commentator: Dr. Lien-I Hor (何漣漪 老師)             Place: Room 601

Abstract

Autophagy is an essential, homeostatic process in which cells break down their own components and is also an important innate immune defense against bacteria infection (1). Autophagy can target invading bacteria pathogens through ubiquitin-LC3 adaptor proteins, which include p62, NDP52, NBR1 and degrade bacteria pathogens via the lysosomal pathway (2). However, some bacterial pathogens can evade autophagy degradation and replicate in the cytosol of infected cells (3). Nevertheless, how bacterial pathogens avoid autophagy to replicate in the cytosol of infected cells remains unknown. Group A streptococcus (GAS) is a strictly human pathogen that normally colonizes the throat and skin without causing disease. The M1T1⁵⁴⁴⁸ strain is the most frequently isolated serotype from patients with invasive and noninvasive cases of GAS infection. The author investigated how M1T1⁵⁴⁴⁸ strain evades autophagy in infected cells. First, when compared with the infection of a laboratory adapted M6^JRS4 strain in HEp-2 epithelial cell, the M1T1⁵⁴⁴⁸ strain efficiently replicated as well as survived within epithelial cells. To determine whether M1T1⁵⁴⁴⁸ strain escape autophagy, the author utilized immunofluorescence microscopy to quantify M1T1⁵⁴⁴⁸and M6^JRS4 strain colocalized with ubiquitylated proteins. The results showed that the M1T1⁵⁴⁴⁸ strain could avoid ubiquitin-LC3 adaptor proteins in epithelial cells. Expression of SpeB, a streptococcal cysteine protease, appears to participate in evasion of autophagy. A M1T1⁵⁴⁴⁸∆speB mutant displayed reduce replication ability and can be targeted by autophagy. Moreover, purified SpeB can degrade ubiquitin-LC3 adaptor proteins in vitro and in host cells. In conclusion, the studies revealed a proteolytic mechanism exploited by GAS to escape host autophagy.

References

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2. Nakagawa et al., Autophagy Defends Cells Against Invading Group A Streptococcus. Science 5 November 2004; 306 (5698): 1037-1040
3. Dortet et al., Recruitment of the Major Vault Protein by InlK: A Listeria monocytogenes Strategy to Avoid Autophagy. PLoS Pathog. 2011 Aug; 7(8):e1002168.