A 群链球菌 M1T1 克隆在全球传播，逃避自噬作用进行细胞内复制。
The globally disseminated M1T1 clone of group A Streptococcus evades autophagy for intracellular replication.
机构信息
Australian Infectious Diseases Research Centre, The University of Queensland, Queensland, St Lucia, QLD 4072, Australia; School of Chemistry and Molecular Biosciences, The University of Queensland, Queensland, St Lucia, QLD 4072, Australia.
Institute for Molecular Bioscience, The University of Queensland, Queensland, St Lucia, QLD 4072, Australia.
出版信息
Cell Host Microbe. 2013 Dec 11;14(6):675-82. doi: 10.1016/j.chom.2013.11.003.
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.
自噬被报道是一种重要的先天免疫防御机制，可抵抗细胞内细菌病原体 A 群链球菌（GAS）。然而，迄今为止检查的 GAS 菌株属于与人类疾病关联不频繁的血清型。我们发现，GAS 的全球传播血清型 M1T1 克隆可以逃避自噬，并在感染细胞的细胞质中有效复制。细胞质中的 M1T1 GAS（菌株 5448），而不是 M6 GAS（菌株 JRS4），可以避免被宿主自噬标志物 LC3 和泛素-LC3 衔接蛋白 NDP52、p62 和 NBR1 泛素化和识别。胞质 SpeB 的表达对这个过程至关重要，因为一个同源 M1T1 ΔspeB 突变株被靶向自噬，并减弱了细胞内复制能力。SpeB 在体外和宿主细胞质中降解 p62、NDP52 和 NBR1。这些结果揭示了 GAS 逃避宿主自噬途径的一种蛋白水解机制，这可能是 M1T1 克隆成功的基础。
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