Ca2+-dependent repair of pneumolysin pores: A new paradigm for host cellular defense against bacterial pore-forming toxins

Draeger, Annette; Schönauer, Roman; Babiychuk, Eduard; Atanassoff, Alexander P.; Wolfmeier, Heidi Annemarie (2015). Ca2+-dependent repair of pneumolysin pores: A new paradigm for host cellular defense against bacterial pore-forming toxins. Biochimica et biophysica acta - molecular cell research, 1853(9), pp. 2045-2054. Elsevier 10.1016/j.bbamcr.2014.09.005

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Pneumolysin (PLY), a key virulence factor of Streptococcus pneumoniae, permeabilizes eukaryotic cells by forming large trans-membrane pores. PLY imposes a puzzling multitude of diverse, often mutually excluding actions on eukaryotic cells. Whereas cytotoxicity of PLY can be directly attributed to the pore-mediated effects, mechanisms that are responsible for the PLY-induced activation of host cells are poorly understood. We show that PLY pores can be repaired and thereby PLY-induced cell death can be prevented. Pore-induced Ca2+ entry from the extracellular milieu is of paramount importance for the initiation of plasmalemmal repair. Nevertheless, active Ca2+ sequestration that prevents excessive Ca2+ elevation during the execution phase of plasmalemmal repair is of no less importance. The efficacy of plasmalemmal repair does not only define the fate of targeted cells but also intensity, duration and repetitiveness of PLY-induced Ca2+ signals in cells that were able to survive after PLY attack. Intracellular Ca2+ dynamics evoked by the combined action of pore formation and their elimination mimic the pattern of receptor-mediated Ca2+ signaling, which is responsible for the activation of host immune responses. Therefore, we postulate that plasmalemmal repair of PLY pores might provoke cellular responses that are similar to those currently ascribed to the receptor-mediated PLY effects. Our data provide new insights into the understanding of the complexity of cellular non-immune defense responses to a major pneumococcal toxin that plays a critical role in the establishment and the progression of life-threatening diseases. Therapies boosting plasmalemmal repair of host cells and their metabolic fitness might prove beneficial for the treatment of pneumococcal infections.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Anatomy
04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Anatomy > Cell Biology

UniBE Contributor:

Draeger, Annette; Schönauer, Roman; Babiychuk, Eduard; Atanassoff, Alexander P. and Wolfmeier, Heidi Annemarie

ISSN:

0167-4889

Publisher:

Elsevier

Language:

English

Submitter:

Annette Draeger

Date Deposited:

06 Jan 2015 17:23

Last Modified:

09 Sep 2017 20:39

Publisher DOI:

10.1016/j.bbamcr.2014.09.005

BORIS DOI:

10.7892/boris.61429

URI:

https://boris.unibe.ch/id/eprint/61429

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