Granulysin, a T cell product, kills bacteria by altering membrane permeability

W. A. Ernst, S. Thoma-Uszynski, R. Teitelbaum, C. Ko, D. A. Hanson, C. Clayberger, A. M. Krensky, M. Leippe, B. R. Bloom, T. Ganz, R. L. Modlin*

*Corresponding author for this work

Research output: Contribution to journalArticle

166 Scopus citations

Abstract

Granulysin, a protein located in the acidic granules of human NK cells and cytotoxic T cells, has antimicrobial activity against a broad spectrum of microbial pathogens. A predicted model generated from the nuclear magnetic resonance structure of a related protein, NK lysin, suggested that granulysin contains a four α helical bundle motif, with the α helices enriched for positively charged amino acids, including arginine and lysine residues. Denaturation of the polypeptide reduced the α helical content from 49 to 18% resulted in complete inhibition of antimicrobial activity. Chemical modification of the arginine, but not the lysine, residues also blocked the antimicrobial activity and interfered with the ability of granulysin to adhere to Escherichia coli and Mycobacterium tuberculosis. Granulysin increased the permeability of bacterial membranes, as judged by its ability to allow access of cytosolic β-galactosidase to its impermeant substrate. By electron microscopy, granulysin triggered fluid accumulation in the periplasm of M. tuberculosis, consistent with osmotic perturbation. These data suggest that the ability of granulysin to kill microbial pathogens is dependent on direct interaction with the microbial cell wall and/or membrane, leading to increased permeability and lysis.

Original languageEnglish (US)
Pages (from-to)7102-7108
Number of pages7
JournalJournal of Immunology
Volume165
Issue number12
DOIs
StatePublished - Dec 15 2000

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Ernst, W. A., Thoma-Uszynski, S., Teitelbaum, R., Ko, C., Hanson, D. A., Clayberger, C., Krensky, A. M., Leippe, M., Bloom, B. R., Ganz, T., & Modlin, R. L. (2000). Granulysin, a T cell product, kills bacteria by altering membrane permeability. Journal of Immunology, 165(12), 7102-7108. https://doi.org/10.4049/jimmunol.165.12.7102