The Extracytoplasmic Linker Peptide of the Sensor Protein SaeS Tunes the Kinase Activity Required for Staphylococcal Virulence in Response to Host Signals

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A bacterial pathogen Staphylococcus aureus uses the SaeRS two-component system to control the production of multiple toxins, resulting in a wide range of diseases in human. The sensor kinase SaeS is a member of the intramembrane-sensing histidine kinases (IM-HKs) that lacks a sensory domain and harbors a simple N-terminal domain with two transmembrane helices and a short linker peptide. It’s been considered that the linker peptide of IM-HKs transmits the external signals into the cytoplasmic catalytic domain to control the HK’s kinase activity. However, it is unclear how the external signal input propagates through the linker to modulate the kinase activity of HKs. Here we show that the linker peptide of SaeS is critical in maintaining the basal kinase activity and functions as a part of a “tripwire” to jumpstart the activation of the SaeRS system upon exposure to the specific host signals. We establish that a single amino acid substitution of the linker peptide alters SaeS’s kinase activity, resulting in different expression levels of the SaeR-activated genes and alteration of the bacterial virulence in mice. Our study provides new molecular insights into how the pathogenic bacterium utilizes the simple protein domain to control its disease-causing potentials in response to host immune signals.

Vyšlo v časopise: The Extracytoplasmic Linker Peptide of the Sensor Protein SaeS Tunes the Kinase Activity Required for Staphylococcal Virulence in Response to Host Signals. PLoS Pathog 11(4): e32767. doi:10.1371/journal.ppat.1004799
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004799

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