Kleine Britta, Chattopadhyay Ava, Polen Tino, Pinto Daniela, Mascher Thorsten, Bott Michael, Brocker Melanie, Freudl Roland
Institut für Bio- und Geowissenschaften 1, Biotechnologie, Forschungszentrum Jülich GmbH, Jülich D-52425, Germany.
Institut für Mikrobiologie, Technische Universität Dresden, Zellescher Weg 20b, Dresden D-01217, Germany.
Mol Microbiol. 2017 Dec;106(5):719-741. doi: 10.1111/mmi.13839. Epub 2017 Oct 12.
When the cell envelope integrity is compromised, bacteria trigger signaling cascades resulting in the production of proteins that counteract these extracytoplasmic stresses. Here, we show that the two-component system EsrSR regulates a cell envelope stress response in the Actinobacterium Corynebacterium glutamicum. The sensor kinase EsrS possesses an amino-terminal phage shock protein C (PspC) domain, a property that sets EsrSR apart from all other two-component systems characterized so far. An integral membrane protein, EsrI, whose gene is divergently transcribed to the esrSR gene locus and which interestingly also possesses a PspC domain, acts as an inhibitor of EsrSR under non-stress conditions. The resulting EsrISR three-component system is activated among others by antibiotics inhibiting the lipid II cycle, such as bacitracin and vancomycin, and it orchestrates a broad regulon including the esrI-esrSR gene locus itself, genes encoding heat shock proteins, ABC transporters, and several putative membrane-associated or secreted proteins of unknown function. Among those, the ABC transporter encoded by cg3322-3320 was shown to be directly involved in bacitracin resistance of C. glutamicum. Since similar esrI-esrSR loci are present in a large number of actinobacterial genomes, EsrISR represents a novel type of stress-responsive system whose components are highly conserved in the phylum Actinobacteria.
当细胞包膜完整性受到损害时，细菌会触发信号级联反应，从而产生能够对抗这些胞外应激的蛋白质。在此，我们表明双组分系统EsrSR可调节放线菌谷氨酸棒杆菌中的细胞包膜应激反应。传感激酶EsrS具有一个氨基末端噬菌体休克蛋白C（PspC）结构域，这一特性使EsrSR有别于迄今为止所表征的所有其他双组分系统。一种整合膜蛋白EsrI，其基因与esrSR基因座反向转录，有趣的是它也具有一个PspC结构域，在非应激条件下作为EsrSR的抑制剂。由此产生的EsrISR三组分系统在其他情况下会被抑制脂质II循环的抗生素（如杆菌肽和万古霉素）激活，它协调一个广泛的调控子，包括esrI-esrSR基因座本身、编码热休克蛋白的基因、ABC转运蛋白以及几种功能未知的假定膜相关或分泌蛋白。其中，由cg3322-3320编码的ABC转运蛋白被证明直接参与谷氨酸棒杆菌对杆菌肽的抗性。由于大量放线菌基因组中存在类似的esrI-esrSR基因座，EsrISR代表了一种新型的应激反应系统，其组分在放线菌门中高度保守。
