5 years ago

The three-component system EsrISR regulates a cell envelope stress response in Corynebacterium glutamicum

The three-component system EsrISR regulates a cell envelope stress response in Corynebacterium glutamicum
Michael Bott, Ava Chattopadhyay, Thorsten Mascher, Britta Kleine, Daniela Pinto, Roland Freudl, Tino Polen, Melanie Brocker
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. This article is protected by copyright. All rights reserved. In many Actinobacteria, a novel and unique type of two-component systems can be found whose hallmark is the presence of a PspC domain in their respective sensor kinases. Here, we elucidated the physiological function of the corresponding two-component system EsrSR of Corynebacterium glutamicum. We show that, together with its negative regulator EsrI, the resulting three-component system EsrISR regulates a broad and diverse cellular response to conditions that threaten the integrity of the cell envelope.

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1111/mmi.13839

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