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The CprRS two-component system regulates virulence in Pseudomonas aeruginosa

ABSTRACT: The ability of Pseudomonas aeruginosa to detect host immune responses and coordinate the production of virulence factors is crucial for its high pathogenicity. However, the regulatory mechanisms underlying this process remain largely unknown. In this study, we extensively characterize the conserved two-component system CprRS in P. aeruginosa and uncover the role of the sensor histidine kinase CprS as a receptor for the human host defense peptide LL-37, thereby modulating bacterial virulence. In the presence of LL-37, CprS functions as a phosphatase, targeting the intracellular activator CprR for phosphorylation at position D53, ultimately leading to CprR activation. By employing quantitative proteomics and transcription analysis, we further elucidate that CprR induction under LL-37 treatment promotes the expression of type III secretion system effectors. This, in turn, impedes the expression of proinflammatory cytokines and significantly increases bacterial cytotoxicity towards macrophages. Notably, the mutation of either cprS or cprR markedly diminishes bacterial survival in both macrophage and insect infection models. Collectively, our study uncovers a novel regulatory mechanism of the two-component system in P. aeruginosa, which enables the bacterium to sense and respond to human innate immune system responses while ensuring a timely balance of virulence genes.

ORGANISM(S): Pseudomonas Aeruginosa Pa14

SUBMITTER: Heyong Xing

PROVIDER: PXD042487 | iProX | Thu May 25 00:00:00 BST 2023

REPOSITORIES: iProX

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