Cholesterol dependent cytolysins and the brain: Revealing a potential therapeutic avenue for bacterial meningitis

Author:

Pramitasuri Tjokorda Istri12,Susilawathi Ni Made3,Tarini Ni Made Adi4,Sudewi AA Raka3,Evans Matthew C56

Affiliation:

1. Doctoral Program in Medical Science, Faculty of Medicine, Universitas Udayana, Bali, Indonesia

2. Postgraduate Research Student, Faculty of Medicine, Imperial College London, United Kingdom

3. Department of Neurology, Faculty of Medicine, Universitas Udayana, Bali, Indonesia

4. Department of Microbiology, Faculty of Medicine, Universitas Udayana-Rumah Sakit Umum Pusat Prof Dr dr IGNG Ngoerah, Bali, Indonesia

5. Pain Research, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, United Kingdom

6. Department of Brain Sciences, Care Research and Technology Centre, UK Dementia Research Institute, London, United Kingdom

Abstract

<abstract> <p>Bacterial meningitis is a catastrophic nervous system disorder with high mortality and wide range of morbidities. Some of the meningitis-causing bacteria occupy cholesterol dependent cytolysins (CDCs) to increase their pathogenicity and arrange immune-evasion strategy. Studies have observed that the relationship between CDCs and pathogenicity in these meningitides is complex and involves interactions between CDC, blood-brain barrier (BBB), glial cells and neurons. In BBB, these CDCs acts on capillary endothelium, tight junction (TJ) proteins and neurovascular unit (NVU). CDCs also observed to elicit intriguing effects on brain inflammation which involves microglia and astrocyte activations, along with neuronal damage as the end-point of pathological pathways in bacterial meningitis. As some studies mentioned potential advantage of CDC-targeted therapeutic mechanisms to combat CNS infections, it might be a fruitful avenue to deepen our understanding of CDC as a candidate for adjuvant therapy to combat bacterial meningitis.</p> </abstract>

Publisher

American Institute of Mathematical Sciences (AIMS)

Subject

Microbiology (medical),Microbiology

Reference131 articles.

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