Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/115588
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Type: Journal article
Title: Streptococcus pneumoniae potently induces cell death in mesothelial cells
Author: Rashwan, R.
Varano della Vergiliana, J.
Lansley, S.
Cheah, H.
Popowicz, N.
Paton, J.
Waterer, G.
Townsend, T.
Kay, I.
Brown, J.
Gary Lee, Y.
Citation: PLoS ONE, 2018; 13(7):e0201530-1-e0201530-15
Publisher: Public Library of Science (PLoS)
Issue Date: 2018
ISSN: 1932-6203
1932-6203
Statement of
Responsibility: 
Rabab Rashwan, Julius F. Varano della Vergiliana, Sally M. Lansley, Hui Min Cheah, Natalia Popowicz, James C. Paton, Grant W. Waterer, Tiffany Townsend, Ian Kay, Jeremy S. Brown, Y. C. Gary Lee
Abstract: Pleural infection/empyema is common and its incidence continues to rise. Streptococcus pneumoniae is the commonest bacterial cause of empyema in children and among the commonest in adults. The mesothelium represents the first line of defense against invading microorganisms, but mesothelial cell responses to common empyema pathogens, including S. pneumoniae, have seldom been studied. We assessed mesothelial cell viability in vitro following exposure to common empyema pathogens. Clinical isolates of S. pneumoniae from 25 patients with invasive pneumococcal disease and three reference strains were tested. All potently induced death of cultured mesothelial cells (MeT-5A) in a dose- and time-dependent manner (>90% at 107 CFU/mL after 24 hours). No significant mesothelial cell killing was observed when cells were co-cultured with Staphylococcus aureus, Streptococcus sanguinis and Streptococcus milleri group bacteria. S. pneumoniae induced mesothelial cell death via secretory product(s) as cytotoxicity could be: i) reproduced using conditioned media derived from S. pneumoniae and ii) in transwell studies when the bacteria and mesothelial cells were separated. No excess cell death was seen when heat-killed S. pneumoniae were used. Pneumolysin, a cytolytic S. pneumoniae toxin, induced cell death in a time- and dose-dependent manner. S. pneumoniae lacking the pneumolysin gene (D39 ΔPLY strain) failed to kill mesothelial cells compared to wild type (D39) controls, confirming the necessity of pneumolysin in D39-induced mesothelial cell death. However, pneumolysin gene mutation in other S. pneumoniae strains (TIGR4, ST3 and ST23F) only partly abolished their cytotoxic effects, suggesting different strains may induce cell death via different mechanisms.
Keywords: Pleura; Epithelium; Cells, Cultured; Epithelial Cells; Humans; Streptococcus pneumoniae; Pneumococcal Infections; Empyema, Pleural; Bacterial Proteins; Streptolysins; Cell Death; Cell Survival; Child
Description: Published: July 30, 2018
Rights: Copyright: © 2018 Rashwan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
RMID: 0030095692
DOI: 10.1371/journal.pone.0201530
Appears in Collections:Microbiology and Immunology publications

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