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

Tjokorda Istri Pramitasuri; Ni Made Susilawathi; Ni Made Adi Tarini; AA Raka Sudewi; Matthew C Evans; Tjokorda Istri Pramitasuri; Ni Made Susilawathi; Ni Made Adi Tarini; AA Raka Sudewi; Matthew C Evans

doi:10.3934/microbiol.2023033

AIMS Microbiology

2023, Volume 9, Issue 4: 647-667. doi: 10.3934/microbiol.2023033

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Mini review

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

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

Received: 18 May 2023 Revised: 24 July 2023 Accepted: 14 August 2023 Published: 21 August 2023

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.
- cholesterol dependent cytolysin,
- bacteria,
- meningitis,
- central nervous system,
- brain
Citation: Tjokorda Istri Pramitasuri, Ni Made Susilawathi, Ni Made Adi Tarini, AA Raka Sudewi, Matthew C Evans. Cholesterol dependent cytolysins and the brain: Revealing a potential therapeutic avenue for bacterial meningitis[J]. AIMS Microbiology, 2023, 9(4): 647-667. doi: 10.3934/microbiol.2023033

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Abstract

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.

Acknowledgments

TIP received scholarship which supports all of her academic works, including the publication of this manuscript from the Directorate of Resources, Directorate General of Higher Education, Ministry of Education, Culture, Research, and Technology, the Republic of Indonesia through Pendidikan Magister Menuju Doktor untuk Sarjana Unggul (PMDSU) scheme. The author thanked Professor Andrew S.C. Rice, MB BS, MD, FRCP, FRCA, FFPMRCA for overall supervision in the process of constructing this manuscript.

Conflict of interest

The authors declare that there were no financial or commercial ties that might be viewed as potential conflicts of interest during the conduct of this manuscript.

Author contributions

TIP, MCE, NMS, NMAT and AARS were involved in overall structure and elaboration of concepts for review. Manuscript writing by TIP and MCE. All authors contributed to editing of manuscript.

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