Active release of pneumolysin prepores and pores by mammalian cells undergoing a Streptococcus pneumoniae attack.

Wolfmeier, Heidi Annemarie; Radecke, Julika; Schönauer, Roman; Köffel, René; Babiychuk, Victoria; Drücker, Patrick; Hathaway, Lucy Jane; Mitchell, Timothy J; Zuber, Benoît; Draeger, Annette; Babiychuk, Eduard (2016). Active release of pneumolysin prepores and pores by mammalian cells undergoing a Streptococcus pneumoniae attack. Biochimica et biophysica acta (BBA) - general subjects, 1860(11 Pt A), pp. 2498-2509. Elsevier 10.1016/j.bbagen.2016.07.022

[img] Text
1-s2.0-S0304416516302690-main.pdf - Published Version
Restricted to registered users only
Available under License Publisher holds Copyright.

Download (1MB) | Request a copy

BACKGROUND Streptococcus pneumoniae is a potent human pathogen. Its pore-forming exotoxin pneumolysin is instrumental for breaching the host's epithelial barrier and for the incapacitation of the immune system. METHODS AND RESULTS Using a combination of life imaging and cryo-electron microscopy we show that pneumolysin, released by cultured bacteria, is capable of permeabilizing the plasmalemma of host cells. However, such permeabilization does not lead to cell lysis since pneumolysin is actively removed by the host cells. The process of pore elimination starts with the formation of pore-bearing plasmalemmal nanotubes and proceeds by the shedding of pores that are embedded in the membrane of released microvesicles. Pneumolysin prepores are likewise removed. The protein composition of the toxin-induced microvesicles, assessed by mass spectrometry, is suggestive of a Ca(2+)-triggered mechanism encompassing the proteins of the annexin family and members of the endosomal sorting complex required for transport (ESCRT) complex. CONCLUSIONS S. pneumoniae releases sufficient amounts of pneumolysin to perforate the plasmalemma of host cells, however, the immediate cell lysis, which is frequently reported as a result of treatment with purified and artificially concentrated toxin, appears to be an unlikely event in vivo since the toxin pores are efficiently eliminated by microvesicle shedding. Therefore the dysregulation of cellular homeostasis occurring as a result of transient pore formation/elimination should be held responsible for the damaging toxin action. GENERAL SIGNIFICANCE We have achieved a comprehensive view of a general plasma membrane repair mechanism after injury by a major bacterial toxin.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Anatomy
04 Faculty of Medicine > Service Sector > Institute for Infectious Diseases
04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Anatomy > Cell Biology
09 Interdisciplinary Units > Microscopy Imaging Center MIC

Graduate School:

Graduate School for Cellular and Biomedical Sciences (GCB)

UniBE Contributor:

Wolfmeier, Heidi Annemarie; Radecke, Julika; Schönauer, Roman; Köffel, René; Babiychuk, Victoria; Drücker, Patrick; Hathaway, Lucy Jane; Zuber, Benoît; Draeger, Annette and Babiychuk, Eduard

Subjects:

600 Technology > 610 Medicine & health
500 Science > 570 Life sciences; biology

ISSN:

0304-4165

Publisher:

Elsevier

Language:

English

Submitter:

Benoît Zuber

Date Deposited:

03 Oct 2016 14:48

Last Modified:

14 Feb 2019 18:03

Publisher DOI:

10.1016/j.bbagen.2016.07.022

PubMed ID:

27481675

Uncontrolled Keywords:

Annexin; Bacterial toxin; Microvesicle; PLY; Plasmalemmal repair; Shedding

BORIS DOI:

10.7892/boris.88801

URI:

https://boris.unibe.ch/id/eprint/88801

Actions (login required)

Edit item Edit item
Provide Feedback