Capsule Contributes to Transmigration of Streptococcus pneumoniae Serotype 7F Meningitis Isolates through Complex Blood Brain Barrier Models

Fuchs, Elena; Untucht, Christopher; Rohde, Manfred

doi:10.4172/2155-9597.1000142

Cited by 3 publications

(3 citation statements)

References 53 publications

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“…A few reports did use encapsulated bacteria to study pneumococci translocation across VEC concluding to a meaningful impact. Fuchs et al found that encapsulated Spn crossed human brain microvascular endothelial cell monolayers more efficiently than their unencapsulated counterparts (44). However, this study focused solely on serotype 7F, did not examine the mechanism, nor include findings with animal models.…”

Section: Discussionmentioning

confidence: 93%

Capsule protects against intracellular killing and enables vascular endothelial cell translocation during invasive pneumococcal disease

Brissac

Martínez

et al. 2021

Preprint

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Streptococcus pneumoniae (Spn) is a leading cause of invasive disease. Chief among its virulence determinants is capsular polysaccharide which protects the bacterium from phagocytosis. While 100 antigenically distinct capsule types are produced by Spn, i.e. serotypes, only 20-30 are commonly associated with invasive disease. A frequency that suggests serotype-specific properties of the capsule influence virulence. Herein, we show capsule has strong antioxidant properties. Moreover, that this property promotes invasive disease by protecting Spn taken up by vascular endothelial cells during bacteremia from endosome-killing and enhancing the translocation rate into organs. Crucially, isogenic capsule-switch mutants of Spn varied considerably in their resistance to H2O2-killing in culture and measured levels correlated positively with intracellular survival rates in vitro, organ invasion rates in vivo, and epidemiologically-established human attack rates for the corresponding serotype. The amount of capsule produced and specific biochemical features of a serotype, such as acetylation, also influenced Spn resistance to oxidative stress. Autolysin-mediated shedding was also found to be necessary, indicating that capsule worked as a distal sink for reactive oxygen species. Our results outline a new role for capsular polysaccharide, as an intracellular antioxidant. They help to explain why certain serotypes of Spn have greater propensity for human disease.

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Section: Discussionmentioning

confidence: 93%

Capsule protects against intracellular killing and enables vascular endothelial cell translocation during invasive pneumococcal disease

Brissac

Martínez

et al. 2021

Preprint

View full text Add to dashboard Cite

show abstract

“…A few reports did use encapsulated bacteria to study pneumococci translocation across VEC, concluding that there was a meaningful impact. Fuchs et al found that encapsulated Spn crossed human brain microvascular endothelial cell monolayers more efficiently than its unencapsulated counterparts ( 52 ). However, this study focused solely on serotype 7F and did not examine the mechanism or include findings with animal models.…”

Section: Discussionmentioning

confidence: 99%

Capsule Promotes Intracellular Survival and Vascular Endothelial Cell Translocation during Invasive Pneumococcal Disease

Brissac

Martínez

Kruckow

et al. 2021

mBio

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“…Various mechanisms of bacterial factors have been established in the penetration of the BBB. The capsule can aid in bacterial transcellular crossing of the BBB, along with other attachment proteins 83 – 85 , 104 , 118 . Other mechanisms of crossing the BBB, including paracellular pathways or the “Trojan horse” mechanism of infected phagocytes, have been identified 83 – 85 , 104 .…”

Section: Pathogenesis Of Meningitismentioning

confidence: 99%

From the microbiome to the central nervous system, an update on the epidemiology and pathogenesis of bacterial meningitis in childhood

Janowski

Newland

2017

F1000Res

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In the past century, advances in antibiotics and vaccination have dramatically altered the incidence and clinical outcomes of bacterial meningitis. We review the shifting epidemiology of meningitis in children, including after the implementation of vaccines that target common meningitic pathogens and the introduction of intrapartum antibiotic prophylaxis offered to mothers colonized with Streptococcus agalactiae. We also discuss what is currently known about the pathogenesis of meningitis. Recent studies of the human microbiome have illustrated dynamic relationships of bacterial and viral populations with the host, which may potentiate the risk of bacterial meningitis.

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Capsule Contributes to Transmigration of Streptococcus pneumoniae Serotype 7F Meningitis Isolates through Complex Blood Brain Barrier Models

Cited by 3 publications

References 53 publications

Capsule protects against intracellular killing and enables vascular endothelial cell translocation during invasive pneumococcal disease

Capsule protects against intracellular killing and enables vascular endothelial cell translocation during invasive pneumococcal disease

Capsule Promotes Intracellular Survival and Vascular Endothelial Cell Translocation during Invasive Pneumococcal Disease

From the microbiome to the central nervous system, an update on the epidemiology and pathogenesis of bacterial meningitis in childhood

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