Granzyme B Attenuates Bacterial Virulence by Targeting Secreted Factors

IScience
Diego López LeónMichael Walch

Abstract

Pathogenic bacteria secrete virulence factors that interact with the human host to establish infections. The human immune system evolved multiple mechanisms to fight bacterial invaders, including immune proteases that were demonstrated to contribute crucially to antibacterial defense. Here we show that granzyme B degrades multiple secreted virulence mediators from Listeria monocytogenes, Salmonella typhimurium, and Mycobacteria tuberculosis. Pathogenic bacteria, when infected in the presence of granzyme B or granzyme-secreting killer cells, fail to grow in human macrophages and epithelial cells owing to their crippled virulence. A granzyme B-uncleavable mutant form of the major Listeria virulence factor, listeriolysin O, rescued the virulence defect in response to granzyme treatment. Hence, we link the degradation of a single factor with the observed decrease in virulent bacteria growth. Overall, we reveal here an innate immune barrier function of granzyme B by disrupting bacterial virulence to facilitate bacteria clearance by bystander immune and non-immune cells.

Citations

Dec 24, 2020·Trends in Microbiology·Edwin LeeansyahJohan K Sandberg
Jul 11, 2021·Clinical and Experimental Allergy : Journal of the British Society for Allergy and Clinical Immunology·Stephany Sánchez-OvandoPeter A B Wark

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Methods Mentioned

BETA
fluorescence microscopy
confocal microscopy
ELISA
gene knockdown

Software Mentioned

GNLY

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