Meningitis-associated pneumococcal serotype 8, ST 53, strain is hypervirulent in a rat model and has non-haemolytic
Annelies Müller1,2, Cebile Lekhuleni3,4, Sabrina Hupp5
1Institute for Infectious Diseases, Faculty of Medicine, University of Bern, Bern, Switzerland.
Introduction:
Streptococcus pneumoniae bacteria cause life-threatening invasive pneumococcal disease (IPD), including meningitis. Pneumococci are classified into serotypes, determined by differences in capsular polysaccharide and both serotype and pneumolysin toxin are associated with disease severity. Strains of serotype 8, ST 53, are increasing in prevalence in IPD in several countries.
Methods:
Here we tested the virulence of such an isolate in a rat model of meningitis in comparison with a serotype 15B and a serotype 14 isolate. All three were isolated from meningitis patients in South Africa in 2019, where serotype 8 is currently the most common serotype in IPD.
Results And Discussion:
Only the serotype 8 isolate was hypervirulent causing brain injury and a high mortality rate. It induced a greater inflammatory cytokine response than either the serotype 15B or 14 strain in the rat model and from primary mixed-glia cells isolated from mouse brains. It had the thickest capsule of the three strains and produced non-haemolytic pneumolysin. Pneumolysin-sequestering liposomes reduced the neuroinflammatory cytokine response in vitro indicating that liposomes have the potential to be an effective adjuvant therapy even for hypervirulent pneumococcal strains with non-haemolytic pneumolysin.
Insights
Serotype 8 Streptococcus pneumoniae caused severe meningitis and brain injury in rats. Liposomes reduced inflammation, showing potential as an adjuvant therapy against hypervirulent pneumococcal strains.
Area of Science:
- Microbiology
- Immunology
- Neuroscience
Background:
- Streptococcus pneumoniae causes invasive pneumococcal disease (IPD), a serious infection including meningitis.
- Pneumococcal serotypes and pneumolysin toxin influence disease severity.
- Serotype 8 strains are increasingly prevalent in IPD globally.
Purpose of the Study:
- To compare the virulence of a prevalent serotype 8 Streptococcus pneumoniae isolate with serotype 14 and 15B isolates in a rat meningitis model.
- To investigate the potential of liposomes as an adjuvant therapy against hypervirulent pneumococcal strains.
Main Methods:
- A rat model of meningitis was used to compare the virulence of serotype 8, 14, and 15B Streptococcus pneumoniae isolates.
- Cytokine responses were measured in vivo and in vitro using primary mouse glial cells.
- The effect of pneumolysin-sequestering liposomes on neuroinflammation was assessed.
Main Results:
- The serotype 8 isolate was hypervirulent, causing high mortality and brain injury in rats.
- Serotype 8 induced a stronger inflammatory cytokine response compared to serotypes 14 and 15B.
- Pneumolysin-sequestering liposomes reduced neuroinflammation in vitro.
Conclusions:
- Serotype 8 Streptococcus pneumoniae isolates are hypervirulent and associated with severe meningitis and brain injury.
- Liposomes show promise as an adjuvant therapy for invasive pneumococcal disease, even against strains with non-haemolytic pneumolysin.
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