Heterogeneity in pneumolysin expression governs the fate of Streptococcus pneumoniae during blood-brain barrier trafficking

Surve, Manalee Vishnu and Bhutda, Smita and Datey, Akshay and Anil, Anjali and Rawat, Shalini and Pushpakaran, Athira and Singh, Dipty and Kim, Kwang Sik and Chakravortty, Dipshikha and Banerjee, Anirban (2018) Heterogeneity in pneumolysin expression governs the fate of Streptococcus pneumoniae during blood-brain barrier trafficking. In: PLOS PATHOGENS, 14 (7).

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Abstract

Outcome of host-pathogen encounter is determined by the complex interplay between protective bacterial and host defense strategies. This complexity further amplifies with the existence of cell-to-cell phenotypic heterogeneity in pathogens which remains largely unexplored. In this study, we illustrated that heterogeneous expression of pneumolysin (Ply), a pore-forming toxin of the meningeal pathogen, S. pneumoniae (SPN) gives rise to stochastically different bacterial subpopulations with variable fate during passage across blood-brain barrier (BBB). We demonstrate that Ply mediated damage to pneumococcus containing vacuolar (PCV) membrane leads to recruitment of cytosolic ``eat-me'' signals, galectin-8 and ubiquitin, targeting SPN for autophagic clearance. However, a majority of high Ply producing subset extensively damages autophagosomes leading to pneumococcal escape into cytosol and efficient clearance by host ubiquitination machinery. Interestingly, a low Ply producing subset halts autophagosomal maturation and evades all intracellular defense mechanisms, promoting its prolonged survival and successful transcytosis across BBB, both in vitro and in vivo. Ply therefore acts as both, sword and shield implying that its smart regulation ensures optimal disease manifestation. Our elucidation of heterogeneity in Ply expression leading to disparate infection outcomes attempts to resolve the dubious role of Ply in pneumococcal pathogenesis.

Item Type:	Journal Article
Publication:	PLOS PATHOGENS
Publisher:	PUBLIC LIBRARY SCIENCE, 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
Additional Information:	Copy right for this article belong to PUBLIC LIBRARY SCIENCE, 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
Department/Centre:	Division of Interdisciplinary Sciences > Centre for Biosystems Science and Engineering
Date Deposited:	23 Aug 2018 15:59
Last Modified:	23 Oct 2018 11:13
URI:	http://eprints.iisc.ac.in/id/eprint/60492

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