A dissemination-prone morphotype enhances extrapulmonary organ entry by Cryptococcus neoformans

Environmental pathogens move from ecological niches to mammalian hosts, requiring adaptation to dramatically different environments. Microbes that disseminate farther, including the fungal meningitis pathogen Cryptococcus neoformans, require additional adaptation to diverse tissues. We demonstrate that the formation of a small C. neoformans morphotype-called seed cells due to their colonizing ability-is critical for extrapulmonary organ entry. Seed cells exhibit changes in fungal cell size and surface expression that result in an enhanced macrophage update. Seed cell formation is triggered by environmental factors, including C. neoformans' environmental niche, and pigeon guano with phosphate plays a central role. Seed cells show the enhanced expression of phosphate acquisition genes, and mutants unable to acquire phosphate fail to adopt the seed cell morphotype. Additionally, phosphate can be released by tissue damage, potentially establishing a feed-forward loop of seed cell formation and dissemination. Thus, C. neoformans' size variation represent inducible morphotypes that change host interactions to facilitate microbe spread.

Automated summary

This research reveals the critical role of seed cells, a small morphotype of Cryptococcus neoformans, in the invasion of extrapulmonary organs. The formation of seed cells is triggered by environmental factors, and they exhibit enhanced interaction with macrophages. Phosphate from pigeon guano plays a central role in the formation of seed cells.