Cryptococcal Meningitis and Anti-virulence Therapeutic Strategies
| Autor: | Kiem Vu, Angela C Gelli, Javier A Garcia |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Microbiology (medical)
Fungal meningitis Environmental Science and Management Phagocytosis Mini Review Central nervous system lcsh:QR1-502 Virulence Blood–brain barrier Microbiology lcsh:Microbiology 03 medical and health sciences medicine 2.2 Factors relating to the physical environment Aetiology 030304 developmental biology Cryptococcus neoformans 0303 health sciences paracellular Innate immune system transcellular biology 030306 microbiology Neurosciences meningitis blood-brain barrier biology.organism_classification medicine.disease virulence medicine.anatomical_structure Infectious Diseases Immunology Soil Sciences Infection Meningitis |
| Zdroj: | Frontiers in Microbiology, Vol 10 (2019) Frontiers in microbiology, vol 10, iss FEB Frontiers in Microbiology |
| Popis: | Fungal infections of the central nervous system are responsible for significant morbidity and mortality. Cryptococcus neoformans (Cn) is the primary cause of fungal meningitis. Infection begins in the lung after inhalation of fungal spores but often spreads to other organs, particularly the brain in immunosuppressed individuals. Cn's ability to survive phagocytosis and endure the onslaught of oxidative attack imposed by the innate immune response facilitates dissemination to the central nervous system (CNS). Despite the success of Cn at bypassing innate immunity, entry into the heavily protected brain requires that Cn overwhelm the highly restricted blood-brain barrier (BBB). This is a formidable task but mounting evidence suggests that Cn expresses surface-bound and secreted virulence factors including urease, metalloprotease, and hyaluronic acid that can undermine the BBB. In addition, Cn can exploit multiple routes of entry to gain access to the CNS. In this review, we discuss the cellular and molecular interface of Cn and the BBB, and we propose that the virulence factors mediating BBB crossing could be targeted for the development of anti-virulence drugs aimed at preventing fungal colonization of the CNS. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|