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Emerging molecular targets in the treatment of bacterial meningitis
1Pediatric Infectious Diseases Division, Johns Hopkins University School of Medicine, 600 North Wolfe Street, Park 256, Baltimore, MD 21287, USA. kwangkim@jhmi.edu
Abstract:
The mortality and morbidity associated with bacterial meningitis have remained significant despite advances in antimicrobial chemotherapy and supportive care. A major contributing factor to this high mortality and morbidity is our incomplete understanding of the pathogenesis of this disease and its associated neurological sequelae. Most cases of bacterial meningitis develop as a result of haematogenous spread, but it is unclear how circulating bacteria cross the blood-brain barrier. Experimental animal studies indicate that two forms of neuronal injury, such as necrotic cortical injury and apoptotic hippocampal injury, are predominant in bacterial meningitis, but the mechanisms by which these two forms of injury occur are unclear. Recent studies have identified several bacteria-host determinants for bacterial translocation of the blood-brain barrier, and several host inflammatory markers that are associated with neuronal injury in animal models of experimental bacterial meningitis. These determinants/markers may provide important targets for the prevention and treatment of bacterial meningitis. This review focuses on representative steps in the pathogenesis of bacterial meningitis that are likely to be key targets in coming years, and summarises the status of current knowledge for each target.
Insights
Bacterial meningitis remains deadly due to poor understanding of its pathogenesis. New research identifies bacterial and host factors influencing blood-brain barrier crossing and neuronal injury, offering potential therapeutic targets.
Area of Science:
- Neuroscience
- Infectious Diseases
- Pathogenesis
Background:
- Bacterial meningitis causes significant mortality and morbidity despite medical advances.
- Incomplete understanding of disease pathogenesis and neurological sequelae contributes to poor outcomes.
- Mechanisms of bacterial translocation across the blood-brain barrier and subsequent neuronal injury remain unclear.
Purpose of the Study:
- To review key steps in bacterial meningitis pathogenesis.
- To summarize current knowledge on bacterial and host determinants of disease.
- To identify potential therapeutic targets for prevention and treatment.
Main Methods:
- Review of recent experimental animal studies.
- Analysis of identified bacteria-host determinants for blood-brain barrier translocation.
- Summary of host inflammatory markers associated with neuronal injury.
Main Results:
- Several bacteria-host determinants facilitate bacterial entry into the central nervous system.
- Specific host inflammatory markers correlate with neuronal damage in meningitis models.
- Understanding these factors is crucial for developing new interventions.
Conclusions:
- Targeting bacterial and host factors involved in pathogenesis may reduce meningitis-related mortality and morbidity.
- Further research into blood-brain barrier crossing and neuronal injury mechanisms is warranted.
- Identifying key determinants offers a pathway for novel therapeutic strategies.