Bacterial pore-forming toxin pneumolysin drives pathogenicity through host extracellular vesicles released during infection

Parveen, S and Bhat, CV and Sagilkumar, AC and Aziz, S and Arya, J and Dutta, A and Dutta, S and Show, S and Sharma, K and Rakshit, S and Johnson, JB and Nongthomba, U and Banerjee, A and Subramanian, K (2024) Bacterial pore-forming toxin pneumolysin drives pathogenicity through host extracellular vesicles released during infection. In: iScience, 27 (8).

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Abstract

Streptococcus pneumoniae is a global priority respiratory pathogen that kills over a million people annually. The pore-forming cytotoxin, pneumolysin (PLY) is a major virulence factor. Here, we found that recombinant PLY as well as wild-type pneumococcal strains, but not the isogenic PLY mutant, upregulated the shedding of extracellular vesicles (EVs) harboring membrane-bound toxin from human THP-1 monocytes. PLY-EVs induced cytotoxicity and hemolysis dose-dependently upon internalization by recipient monocyte-derived dendritic cells. Proteomics analysis revealed that PLY-EVs are selectively enriched in key inflammatory host proteins such as IFI16, NLRC4, PTX3, and MMP9. EVs shed from PLY-challenged or infected cells induced dendritic cell maturation and primed them to infection. In vivo, zebrafish administered with PLY-EVs showed pericardial edema and mortality. Adoptive transfer of bronchoalveolar-lavage-derived EVs from infected mice to healthy recipients induced lung damage and inflammation in a PLY-dependent manner. Our findings identify that host EVs released during infection mediate pneumococcal pathogenesis. © 2024 The Author(s)

Item Type:	Journal Article
Publication:	iScience
Publisher:	Elsevier Inc.
Additional Information:	The copyright for this article belongs to the publisher.
Department/Centre:	Division of Biological Sciences > Molecular Reproduction, Development & Genetics
Date Deposited:	29 Aug 2024 07:05
Last Modified:	29 Aug 2024 07:05
URI:	http://eprints.iisc.ac.in/id/eprint/86006

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