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

PLoS Pathogens
Manalee Vishnu SurveAnirban Banerjee

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 regul...Continue Reading

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Citations

Jun 1, 2019·Future Microbiology·Manalee Vishnu Surve, Anirban Banerjee
Oct 29, 2019·Cellular Microbiology·Loic Le GuennecSandrine Bourdoulous
Nov 24, 2020·Frontiers in Cellular and Infection Microbiology·Anjali Anil, Anirban Banerjee
Jul 26, 2021·Lancet·Diederik van de BeekEmma C Wall
Aug 12, 2021·Trends in Molecular Medicine·Bharathi SundareshTim van Opijnen
Nov 16, 2021·Frontiers in Cellular and Infection Microbiology·Mark A HarrisonLisa F Dawson

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Methods Mentioned

BETA
PCR
flow cytometry
transfections
transfection
confocal microscopy
ubiquitination
fluorescence microcopy
lipidation
Flow

Software Mentioned

Ply
Zen lite
FlowJo
GraphPad Prism

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