Mucor circinelloides Thrives inside the Phagosome through an Atf-Mediated Germination Pathway.
Author/s
Pérez Arques, Carlos; Navarro Mendoza, María Isabel; Murcia Flores, Laura; Lax, Carlos; Martínez García, Pablo; [et al.]Date
2019-02Discipline/s
MedicinaSubject/s
Innate immunityMucormycosis
Emerging pathogens
Abstract
Mucormycosis is an emerging fungal infection that is often lethal due to the ineffectiveness of current therapies. Here, we have studied the first stage of this infection-the germination of Mucor circinelloides spores inside phagocytic cells-from an integrated transcriptomic and functional perspective. A relevant fungal gene network is remodeled in response to phagocytosis, being enriched in crucial functions to survive and germinate inside the phagosome, such as nutritional adaptation and response to oxidative stress. Correspondingly, the phagocytic cells induced a specific proinflammatory and apoptotic response to the pathogenic strain. Deletion of fungal genes encoding putative transcription factors (atf1, atf2, and gcn4), extracellular proteins (chi1 and pps1), and an aquaporin (aqp1) revealed that these genes perform important roles in survival following phagocytosis, germination inside the phagosome, and virulence in mice. atf1 and atf2 play a major role in these pathogenic proce...