Role of neural barriers in the pathogenesis and outcome of Streptococcus pneumoniae meningitis

Abstract

Bacterial meningitis is an inflammatory disease of the meninges of the central nervous system (CNS). Streptococcus pneumoniae (S. pneumoniae), Neisseria meningitidis, and Haemophilus influenzae are the major bacterial pathogens causing meningitis with S. pneumoniae being responsible for two thirds of meningitis cases in the developed world. To reach the CNS following nasopharyngeal colonization and bacteraemia, the bacteria traverse from the circulation across the blood brain barrier (BBB) and choroid plexus. While the BBB has a protective role in healthy individuals by shielding the CNS from neurotoxic substances circulating in the blood and maintaining the homeostasis within the brain environment, dysfunction of the BBB is associated with the pathophysiology of numerous neurologic disorders, including bacterial meningitis. Inflammatory processes, including release of a broad range of cytokines and free radicals, further increase vascular permeability and contribute to the excessive neural damage observed. Injury to the cerebral microvasculature and loss of blood flow auto-regulation promote increased intracranial pressure and may lead to vascular occlusion. Other common complications commonly associated with meningitis include abnormal neuronal hyper-excitability (e.g., seizures) and loss of hearing. Despite the existence of antibiotic treatment and adjuvant therapy, the relatively high mortality rate and the severe outcomes among survivors of pneumococcal meningitis in developing and developed countries increase the urgency in the requirement of discovering novel biomarkers for the early diagnosis as well as novel treatment approaches. The present review aimed to explore the changes in the brain vascular barriers, which allow S. pneumoniae to invade the CNS, and describe the resultant brain injuries following bacterial meningitis.

CSF Levels of Elongation Factor Tu Is Associated With Increased Mortality in Malawian Adults With Streptococcus pneumoniae Meningitis

“…We detected both expansion of the anti-infective components of CSF (immunoglobulins and complement) and high levels of expression of neutrophil-associated proteins including S100A8/ 9, cathepsin, neutrophil defensin, and matrix-metalloproteinases 9 (MMP9) that infection models have suggested are detrimental to the host (Tuomanen et al, 1989;Roine et al, 2014;Mohanty et al, 2019). Severe BBB breakdown has previously been assumed to be a pre-morbid event in PM (Barichello et al, 2011;Prager et al, 2017), and quantifying BBB breakdown in patients is complex (Helms et al, 2016;Prager et al, 2017;Natarajan et al, 2017). In this dataset, which is controlled for protein abundance, the presence of both brain-derived proteins (e.g.…”

Group A Streptococcus Subcutaneous Infection-Induced Central Nervous System Inflammation Is Attenuated by Blocking Peripheral TNF

“…Traditional treatment of S. pneumoniae infection by antibiotic only reduced bacterial load but not be able to rescue neuronal injury (Kadurugamuwa et al, 2005). BBB opening controlled by TNF is necessary for the development of meningitis (Tsao et al, 2002; Prager et al, 2017). Previous studies showed that an inhibitor of TNF-α converting enzyme and MMP efficiently decreased neuronal injury and improved survival without inhibiting bacterial growth (Meli et al, 2004; Echchannaoui et al, 2007).…”

Streptococcus pneumoniae Cell Wall-Localized Trigger Factor Elicits a Protective Immune Response and Contributes to Bacterial Adhesion to the Host

“…NSC 34 38 and U251 39 cell-lines were used due to their neural origin. S. pneumoniae , Neisseria meningitidis and Haemophilus influenzae are the major bacterial pathogens causing meningitis, with S. pneumoniae being responsible for two thirds of meningitis cases in the developed world 54 , 55 . NSC 34 is a mouse neuroblastoma-spinal cord hybrid immortalized cell-line 38 , which has been used to study differentiation and characteristics of motor neuron 56 , 57 .…”