Fungal mechanisms of intracellular survival: what can we learn from bacterial pathogens?

Fungal infections represent a major, albeit neglected, public health threat with serious medical and economic burdens globally. With unacceptably high mortality rates, invasive fungal pathogens are responsible for millions of deaths each year, with a steadily increasing incidence primarily in immunocompromised individuals. The poor therapeutic options and rise of antifungal drug resistance pose further challenges in controlling these infections. These fungal pathogens have adapted to survive within mammalian hosts and can establish intracellular niches to promote survival within host immune cells. To do that, they have developed diverse methods to circumvent the innate immune system attack. This includes strategies such as altering their morphology, counteracting macrophage antimicrobial action, and metabolic adaptation. This is reminiscent of how bacterial pathogens have adapted to survive within host cells and cause disease. However, relative to the great deal of information available concerning intracellular bacterial pathogenesis, less is known about the mechanisms fungal pathogens employ. Therefore, here we review our current knowledge and recent advances in our understanding of how fungi can evade and persist within host immune cells. This review will focus on the major fungal pathogens, including Cryptococcus neoformans, Candida albicans, and Aspergillus fumigatus, among others. As we discover and understand the strategies used by these fungi, similarities with their bacterial counterparts are becoming apparent, hence we can use the abundant information from bacteria to guide our studies in fungi. By understanding these strategies, new lines of research will open that can improve the treatments of these devastating fungal diseases.