AUTHOR=Vu Kiem , Garcia Javier A. , Gelli Angie 

TITLE=Cryptococcal Meningitis and Anti-virulence Therapeutic Strategies

JOURNAL=Frontiers in Microbiology

VOLUME=10

YEAR=2019

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2019.00353

DOI=10.3389/fmicb.2019.00353

ISSN=1664-302X

ABSTRACT=<p>Fungal infections of the central nervous system are responsible for significant morbidity and mortality. <italic>Cryptococcus neoformans</italic> (<italic>Cn</italic>) 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. <italic>Cn</italic>’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 <italic>Cn</italic> at bypassing innate immunity, entry into the heavily protected brain requires that <italic>Cn</italic> overwhelm the highly restricted blood-brain barrier (BBB). This is a formidable task but mounting evidence suggests that <italic>Cn</italic> expresses surface-bound and secreted virulence factors including urease, metalloprotease, and hyaluronic acid that can undermine the BBB. In addition, <italic>Cn</italic> can exploit multiple routes of entry to gain access to the CNS. In this review, we discuss the cellular and molecular interface of <italic>Cn</italic> 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.</p>