ABSTRACT

Fungal infections kill one and a half million people per year worldwide. Cryptococcus neoformans, the leading cause of fungal meningitis, plays a large role in infection of immunocompromised patients, especially those in Sub-Saharan Africa and southeast Asia with HIV/AIDS. Lung macrophages, which present a first line of host defense against C. neoformans infection, provide a glucose-poor environment and non-preferred carbon sources such as acetate are important early in establishment of a pulmonary infection. During growth on acetate or fatty acids, L-carnitine serves as an essential carrier for intracellular transport of acetyl units into the mitochondria for metabolism via the tricarboxylic acid cycle. Thus, it is likely the synthesis/transport of L-carnitine is vital during infection.

This study examines the biosynthetic pathway of L-carnitine in various pathogenic fungi and determines this pathway’s role in the virulence of C. neoformans. Genomic databases describe which pathogenic fungi contain the pathway. Additionally, sequence alignment programs analyzed which amino acids are valuable for protein/enzyme function. Finally, theoretical mitochondrial targeting sequence programs determined the pathway’s location. After examining the enzymes and transporters of the L-carnitine pathway one may use the data to predict virulence in pathogenic fungi and eventually develop antifungal treatments.