Streptococcus pneumoniae potently induces cell death in mesothelial cells

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 resp...

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Bibliographic Details
Published in:PloS one 2018-07, Vol.13 (7), p.e0201530-e0201530
Main Authors: Rashwan, Rabab, Varano Della Vergiliana, Julius F, Lansley, Sally M, Cheah, Hui Min, Popowicz, Natalia, Paton, James C, Waterer, Grant W, Townsend, Tiffany, Kay, Ian, Brown, Jeremy S, Lee, Y C Gary
Format: Article
Language:English
Subjects:
Adults
Apoptosis
Bacteria
Biology and Life Sciences
Cell death
Children
Clinical isolates
Conditioning
Cytokines
Cytotoxicity
Empyema
Hospitals
Infectious diseases
Medicine
Medicine and Health Sciences
Mesothelium
Microorganisms
Mortality
Mutation
Pathogens
Pharmacology
Pneumolysin
Point mutation
Strains (organisms)
Streptococcus
Streptococcus infections
Streptococcus pneumoniae
Time dependence
Toxicity
Vaccines
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Summary: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.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0201530