Meningitis-associated pneumococcal serotype 8, ST 53, strain is hypervirulent in a rat model and has non-haemolytic pneumolysin which can be attenuated by liposomes

Müller, Annelies; Lekhuleni, Cebile; Hupp, Sabrina; du Plessis, Mignon; Holivololona, Lalaina; Babiichuk, Eduard; Leib, Stephen L.; Grandgirard, Denis; Iliev, Asparouh I.; von Gottberg, Anne; Hathaway, Lucy J. (2023). Meningitis-associated pneumococcal serotype 8, ST 53, strain is hypervirulent in a rat model and has non-haemolytic pneumolysin which can be attenuated by liposomes. Frontiers in cellular and infection microbiology, 12 Frontiers 10.3389/fcimb.2022.1106063

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

09 Interdisciplinary Units > Microscopy Imaging Center (MIC)
04 Faculty of Medicine > Service Sector > Institute for Infectious Diseases > Research
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 > Functional Anatomy

Graduate School:

Graduate School for Cellular and Biomedical Sciences (GCB)

UniBE Contributor:

Müller, Annelies Kathrin, Hupp, Sabrina, Holivololona, Lalaina, Babiichuk, Eduard, Leib, Stephen, Grandgirard, Denis, Iliev, Asparouh Iliev, Hathaway, Lucy Jane

Subjects:

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

ISSN:

2235-2988

Publisher:

Frontiers

Funders:

[UNSPECIFIED] Swiss-South African Joint Research Programme ; [4] Swiss National Science Foundation ; [UNSPECIFIED] Fogarty International Center Global Infectious Disease research training grant

Projects:

[UNSPECIFIED] 170844
[UNSPECIFIED] 310030_189136

Language:

English

Submitter:

Lucy Jane Hathaway

Date Deposited:

17 Jan 2023 10:31

Last Modified:

19 Sep 2024 14:28

Publisher DOI:

10.3389/fcimb.2022.1106063

BORIS DOI:

10.48350/177091

URI:

https://boris.unibe.ch/id/eprint/177091

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