Pneumococcal hydrogen peroxide regulates host cell kinase activity.
Jasmin Bazant1, Astrid Weiss2, Julia Baldauf2
1Institute of Medical Microbiology, German Centre for Infection Giessen-Marburg-Langen Site, Justus-Liebig University Giessen, Giessen, Germany.
Frontiers in Immunology
|June 21, 2024
Summary
Pneumococcal hydrogen peroxide (H2O2) significantly alters lung cell protein kinase activity. Lower H2O2 levels from a mutant Streptococcus pneumoniae strain prevented widespread kinase downregulation, including key kinases like Akt1 and Lck.
Area of Science:
- Cellular Biology
- Microbiology
- Immunology
Background:
- Protein kinases regulate cellular processes and are affected by bacterial infections.
- Streptococcus pneumoniae (Spn) impacts host cell phosphorylation, but the specific mediator is unknown.
- Hydrogen peroxide (H2O2) is a key bacterial product with potential signaling roles.
Purpose of the Study:
- To investigate the influence of pneumococcal H2O2 on protein kinase activity in human lung epithelial cells (H441).
- To determine if H2O2 is the mediator of Spn-induced changes in kinase activity.
Main Methods:
- Kinome analysis using PamGene microarray chips.
- Protein analysis via Western blotting.
- Infection of H441 cells with wild-type Spn (SpnWT) and an H2O2-deficient mutant (SpnΔlctOΔspxB).
Main Results:
- Kinase activity profiles in H441 cells varied significantly based on pneumococcal H2O2 levels.
- Widespread kinase downregulation observed with SpnWT infection was absent when using the H2O2-deficient mutant.
- Specific H2O2-mediated effects identified: downregulation of Protein kinase B (Akt1) and activation of lymphocyte-specific tyrosine protein kinase (Lck).
Conclusions:
- Pneumococcal H2O2 is a key mediator of altered host cell kinase activity during infection.
- H2O2 directly influences the phosphorylation status of critical kinases like Akt1 and Lck.
- Understanding these H2O2-driven signaling changes is crucial for addressing Spn pathogenesis.
Related Concept Videos
02:54Protein Kinases and Phosphatases
13.1K
Proteins undergo chemical modifications that trigger changes in the charge, structure, and conformation of the proteins. Phosphorylation, acetylation, glycosylation, nitrosylation, ubiquitination, lipidation, methylation, and proteolysis are various protein modifications that regulate protein activity. Such modifications are usually enzyme-driven.
Protein kinases
Many proteins in the cell are regulated by phosphorylation, the addition of a phosphate group. A family of enzymes called kinases...
Protein kinases
Many proteins in the cell are regulated by phosphorylation, the addition of a phosphate group. A family of enzymes called kinases...
13.1K
01:24Peroxisomes
12.0K
Peroxisomes are specialized organelles present in fungi, plant, and animal cells. It can vary in number, size, morphology, and activity depending on the type of tissue and the nutritional state of the cell. For example, cells with active lipid metabolism, such as adipocytes, neurons, and hepatocytes, have more peroxisomes than other cells in the body. Besides their primary role in breaking down complex organic molecules, peroxisomes can also synthesize specific macromolecules and participate in...
12.0K
01:22PI3K/mTOR/AKT Signaling Pathway
3.5K
The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast, mTORC2 consists of a...
3.5K
01:22Amplifying Signals via Enzymatic Cascade
8.5K
When a ligand binds to a cell-surface receptor, the receptor's intracellular domain changes shape, which may either activate its enzyme function or allow its binding to other molecules. The initial signal is amplified by most signal transduction pathways. This means that a single ligand molecule can activate multiple molecules of a downstream target. Proteins that relay a signal are most commonly phosphorylated at one or more sites, activating or inactivating the protein. Kinases catalyze...
8.5K
01:23Negative Regulator Molecules
35.3K
Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.
35.3K
02:34Inhibition of Cdk Activity
4.7K
The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
4.7K