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Invasion of Human Cells by a Bacterial Pathogen
Published on: March 21, 2011
Granulysin, a T cell product, kills bacteria by altering membrane permeability
W A Ernst1, S Thoma-Uszynski, R Teitelbaum
1Division of Dermatology, Division of Pulmonary Medicine, Department of Microbiology and Immunology, and Molecular Biology Institute, University of California School of Medicine, Los Angeles, CA 90095, USA.
Journal of Immunology (Baltimore, Md. : 1950)
|December 20, 2000
Summary
Granulysin, an antimicrobial protein from immune cells, kills pathogens by disrupting their cell membranes. Its antimicrobial activity relies on its structure and arginine residues for effective pathogen interaction.
Area of Science:
- Immunology
- Microbiology
- Structural Biology
Background:
- Granulysin is a protein found in human natural killer (NK) cells and cytotoxic T cells.
- It exhibits broad-spectrum antimicrobial activity against various pathogens.
- Structural predictions suggest a four alpha helical bundle motif rich in charged amino acids.
Purpose of the Study:
- To investigate the structural basis of granulysin's antimicrobial activity.
- To determine the role of specific amino acid residues and protein structure in its function.
- To elucidate the mechanism by which granulysin interacts with and kills microbial pathogens.
Main Methods:
- Protein denaturation to assess the impact on alpha helical content and antimicrobial activity.
- Chemical modification of arginine and lysine residues to evaluate their role.
- Assays to measure bacterial membrane permeability using ss-galactosidase.
- Electron microscopy to visualize granulysin's effect on bacterial cell structure.
Main Results:
- Reduced alpha helical content (from 49% to 18%) upon denaturation completely inhibited antimicrobial activity.
- Chemical modification of arginine residues, but not lysine, abolished antimicrobial activity and adhesion to bacteria.
- Granulysin increased bacterial membrane permeability, allowing cytosolic enzyme access to its substrate.
- Electron microscopy showed granulysin induced periplasmic fluid accumulation in Mycobacterium tuberculosis, suggesting osmotic perturbation.
Conclusions:
- Granulysin's antimicrobial function is critically dependent on its structural integrity, specifically its alpha helical content.
- Arginine residues are essential for granulysin's antimicrobial activity and its ability to adhere to microbial surfaces.
- Granulysin kills pathogens by directly interacting with their cell wall/membrane, increasing permeability and causing lysis.
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