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Article
| Open AccessIntegrating central nervous system metagenomics and host response for diagnosis of tuberculosis meningitis and its mimics
Tuberculous meningitis is difficult to differentiate from meningitis caused by other pathogens. Here, the authors combine metagenomics-based pathogen detection in cerebrospinal fluid with a host gene expression-based machine learning classifier for diagnosis.
- P. S. Ramachandran
- , A. Ramesh
- & M. R. Wilson
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Article
| Open AccessNeutrophil extracellular traps in the central nervous system hinder bacterial clearance during pneumococcal meningitis
Neutrophils play critical roles in the host response to bacteria, including the production neutrophil extracellular traps (NET). Here the authors show that NET formation in the context of pneumococcal meningitis impairs bacterial clearance and targeting NET formation in this context could be a potential therapeutic option.
- Tirthankar Mohanty
- , Jane Fisher
- & Adam Linder
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Article
| Open AccessGenome-wide association analyses of invasive pneumococcal isolates identify a missense bacterial mutation associated with meningitis
Meningitis is a severe form of invasive pneumococcal disease (IPD). To study the contribution of bacterial genomic variation, here Li et al. perform whole genome sequencing of pneumococcal isolates from IPD patients and identify an association for higher risk of meningitis with a pbp1bA641C variant
- Yuan Li
- , Benjamin J. Metcalf
- & Bernard W. Beall
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Article
| Open AccessA mouse model reproducing the pathophysiology of neonatal group B streptococcal infection
Animal models of group-B streptococcal infections are needed to develop effective therapies. Here, Andrade et al. present a mouse model in which the bacteria are transmitted from vaginally colonised pregnant females to their offspring, causing neonatal meningitis and neurological developmental disabilities.
- Elva Bonifácio Andrade
- , Ana Magalhães
- & Paula Ferreira
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Article
| Open AccessStructure-based design of chimeric antigens for multivalent protein vaccines
Factor H binding protein (fHbp) and PorA are components of experimental serogroup B N. meningitidis vaccines. Here the authors graft the VR2 loop of PorA onto an fHBp-based scaffold to demonstrate proof-of-principle of a chimeric antigen strategy and vaccination against meningococcal disease.
- S. Hollingshead
- , I. Jongerius
- & C. M. Tang
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Article
| Open AccessCrystal structure reveals vaccine elicited bactericidal human antibody targeting a conserved epitope on meningococcal fHbp
Factor H binding protein (fHbp) is a meningococcal virulence factor and a component of vaccines against serogroup B Neisseria meningitidis. Here, the authors characterize the vaccine-elicited human antibody Fab 1A12 and present both the free and the fHbp-bound Fab 1A12 crystal structures.
- Jacinto López-Sagaseta
- , Peter T. Beernink
- & Matthew J. Bottomley
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Article |
gp96 expression in neutrophils is critical for the onset of Escherichia coli K1 (RS218) meningitis
E. coliK1 can elude the innate immune system and cause neonatal meningitis. This study shows thatE. coli K1 enters polymorphonuclear leukocytes (PMNs) using gp96 to reduce the oxidative burst, and that PMN-depleted mice are resistant to E. coliK1 infection, suggesting that PMNs permit bacterial survival in the host.
- Rahul Mittal
- & Nemani V. Prasadarao