Pneumococcal hydrogen peroxide regulates host cell kinase activity.

Introduction: Protein kinases are indispensable reversible molecular switches that adapt and control protein functions during cellular processes requiring rapid responses to internal and external events. Bacterial infections can affect kinase-mediated phosphorylation events, with consequences for both innate and adaptive immunity, through regulation of antigen presentation, pathogen recognition, cell invasiveness and phagocytosis. Streptococcus pneumoniae ( Spn ), a human respiratory tract pathogen and a major cause of community-acquired pneumoniae, affects phosphorylation-based signalling of several kinases, but the pneumococcal mediator(s) involved in this process remain elusive. In this study, we investigated the influence of pneumococcal H ₂ O ₂ on the protein kinase activity of the human lung epithelial H441 cell line, a generally accepted model of alveolar epithelial cells.
Methods: We performed kinome analysis using PamGene microarray chips and protein analysis in Western blotting in H441 lung cells infected with Spn wild type ( SpnWT ) or with SpnΔlctOΔspxB -a deletion mutant strongly attenuated in H ₂ O ₂ production- to assess the impact of pneumococcal hydrogen peroxide (H ₂ O ₂ ) on global protein kinase activity profiles.
Results: Our kinome analysis provides direct evidence that kinase activity profiles in infected H441 cells significantly vary according to the levels of pneumococcal H ₂ O ₂ . A large number of kinases in H441 cells infected with SpnWT are significantly downregulated, whereas this no longer occurs in cells infected with the mutant SpnΔlctOΔspxB strain, which lacks H ₂ O _2. In particular, we describe for the first time H ₂ O ₂ -mediated downregulation of Protein kinase B (Akt1) and activation of lymphocyte-specific tyrosine protein kinase (Lck) via H ₂ O ₂ -mediated phosphorylation.
Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision.
(Copyright © 2024 Bazant, Weiss, Baldauf, Schermuly, Hain, Lucas and Mraheil.)