Human neutrophil defensin-1 binding increases histidine kinase activity of SaeS in Staphylococcus aureus

Human neutrophil defensin-1 (HNP-1) can specifically activate the SaeRS two-component system(TCS), which is essential for controlling virulence and immune evasion factors in Staphylococcus aureus. The reaction to HNP1 requires the transmembrane domain of SaeS (SaeS™), however the precise mechanism i...

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Main Authors: Zhengfei Qi, Shuru Lin, Quanxiang Yu, Rui Ma, Kexin Zhang, Wenqi Jiang, Shurong Chen, Yilin Mai, Qingshan Bill Fu
Format: Article
Language:English
Published: Elsevier 2025-06-01
Series:Biochemistry and Biophysics Reports
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Online Access:http://www.sciencedirect.com/science/article/pii/S240558082500069X
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Summary:Human neutrophil defensin-1 (HNP-1) can specifically activate the SaeRS two-component system(TCS), which is essential for controlling virulence and immune evasion factors in Staphylococcus aureus. The reaction to HNP1 requires the transmembrane domain of SaeS (SaeS™), however the precise mechanism is yet unknown. In this work, we reconstructed the SaeS™ protein into bicelles and discovered that HNP1 can interact directly with SaeS™ using BiacoreT200, their binding significantly increases SaeS kinase activity and activated the SaeRS system subsequently. Staphylococcus aureus may exploit host-derived factors released by human immune cells to activate its two-component signal transduction system, thereby enhancing antimicrobial peptide resistance.
ISSN:2405-5808