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Updated: Feb 7, 2026
Capsular Serotyping of Streptococcus pneumoniae Using the Quellung Reaction
Published on: February 24, 2014
Streptococcus pneumoniae potently induces cell death in mesothelial cells
Rabab Rashwan1,2, Julius F Varano Della Vergiliana1,3, Sally M Lansley1,3
1Centre for Respiratory Health, University of Western Australia, Perth, Western Australia, Australia.
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.
Insights
Streptococcus pneumoniae causes significant mesothelial cell death in pleural infections. This bacterial toxin, pneumolysin, is key, though other S. pneumoniae strains may use different mechanisms.
Area of Science:
- * Infectious Diseases
- * Cell Biology
- * Microbiology
Background:
- * Pleural infection (empyema) is a growing concern, frequently caused by Streptococcus pneumoniae.
- * Mesothelial cells are the primary defense against pathogens but their response to empyema bacteria is poorly understood.
- * Understanding mesothelial cell interactions is crucial for empyema pathogenesis.
Purpose of the Study:
- * To investigate the impact of common empyema pathogens on mesothelial cell viability.
- * To elucidate the mechanisms by which Streptococcus pneumoniae induces mesothelial cell death.
Main Methods:
- * In vitro assessment of mesothelial cell (MeT-5A) viability upon exposure to clinical and reference strains of S. pneumoniae.
- * Co-culture experiments with Staphylococcus aureus and Streptococcus milleri group bacteria.
- * Analysis of cytotoxicity using conditioned media, transwell systems, heat-killed bacteria, and pneumolysin-deficient S. pneumoniae strains.
Main Results:
- * S. pneumoniae potently induced mesothelial cell death in a dose- and time-dependent manner (>90% cell death at 107 CFU/mL after 24 hours).
- * Other tested bacteria (S. aureus, S. sanguinis, S. milleri group) did not cause significant mesothelial cell killing.
- * S. pneumoniae-mediated cytotoxicity was primarily due to secretory products, particularly the toxin pneumolysin.
- * A pneumolysin-deficient S. pneumoniae strain (D39 ΔPLY) failed to induce cell death, confirming pneumolysin's role.
- * Pneumolysin gene mutations in other strains only partially reduced cytotoxicity, suggesting strain-specific mechanisms.
Conclusions:
- * Streptococcus pneumoniae actively kills mesothelial cells, a key component of the pleural defense barrier.
- * Pneumolysin is a major virulence factor responsible for S. pneumoniae-induced mesothelial cell death.
- * Different S. pneumoniae strains may employ diverse mechanisms to induce mesothelial cell death, warranting further investigation.
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