The cause and effect of Cryptococcus interactions with the host

Abstract

Upon Cryptococcus neoformans infection of the host lung, the fungus enters a nutrient poor environment and must adapt to a variety of host-specific stress conditions (temperature, nutrient limitation, pH, CO). Fungal spores enter this milieu with limited nutritional reserves, germinate, and begin proliferating by budding as yeast. Although relatively little is known about the initial stages of infection, recent work has characterized changes that occur upon germination. This program and subsequent yeast-phase proliferation progress in a dynamic environment as host nutrient immunity responds to the infection via toxic accumulation or sequestration of essential micronutrients and innate immune cells are recruited to the site of infection. Adaptation to the host environment and evasion of the immune response through pathogenicity factor expression allows proliferation and dissemination to multiple sites throughout the body, including, most significantly for human disease, the central nervous system. Here we will discuss recent insights into mechanisms underlying C. neoformans interactions with the host during infection.

Regulated Release of Cryptococcal Polysaccharide Drives Virulence and Suppresses Immune Cell Infiltration into the Central Nervous System

“…S4E to G). We did not observe any interpretable differences in exo-GXM levels on a per-cell basis (data not shown), possibly due to changing host conditions over the course of dissemination ( 46 , 50 , 51 ). For instance, the amount of GXM per CFU fluctuated greatly in the lungs and extrapulmonary organs over the course of infection (Fig.…”

Role of Amino Acid Metabolism in the Virulence of Human Pathogenic Fungi

“…Besides the primary virulence factors, which have been studied more extensively, metabolic versatility represents an integral part of fungal pathogenicity, since it provides the platform for nutrient assimilation and adaptation to host-imposed stress and antifungal drugs [2][3][4][5][6][7][8][9][10][11][12][13]. For the pathogenic fungi reviewed here, metabolic adaptations have evolved dependent on their environmental reservoir, generating the basis for the differences in nutrient utilization.…”

The Cryptococcus neoformans Titan Cell: From In Vivo Phenomenon to In Vitro Model

“…Consistent with this, loss of the cell cycle-responsive transcription factor USV101 increases the frequency at which cells make the yeast-to-Titan switch [6••, 45]. We have recently reviewed progress on the interaction of the cell cycle with C. neoformans virulence and suggest that Titanization is similarly regulated at the level of the cell cycle [57]. A mechanistic understanding of how the above conditions influence these events is clearly needed.…”