Show simple item record

dc.contributor.authorPérez Arques, Carlos
dc.contributor.authorNavarro Mendoza, María Isabel
dc.contributor.authorMurcia Flores, Laura
dc.contributor.authorLax, Carlos
dc.contributor.authorMartínez García, Pablo
dc.contributor.authorHeitman, Joseph
dc.contributor.authorNicolás, Francisco Esteban
dc.contributor.authorGarre, Victoriano
dc.date.accessioned2024-02-05T07:57:46Z
dc.date.available2024-02-05T07:57:46Z
dc.date.issued2019-02
dc.identifier.urihttp://hdl.handle.net/10952/7201
dc.description.abstractMucormycosis 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 processes, since their mutants showed the strongest phenotypes and both genes control a complex gene network of secondarily regulated genes, including chi1 and aqp1 These new insights into the initial phase of mucormycosis define genetic regulators and molecular processes that could serve as pharmacological targets.IMPORTANCE Mucorales are a group of ancient saprophytic fungi that cause neglected infectious diseases collectively known as mucormycoses. The molecular processes underlying the establishment and progression of this disease are largely unknown. Our work presents a transcriptomic study to unveil the Mucor circinelloides genetic network triggered in fungal spores in response to phagocytosis by macrophages and the transcriptional response of the host cells. Functional characterization of differentially expressed fungal genes revealed three transcription factors and three extracellular proteins essential for the fungus to survive and germinate inside the phagosome and to cause disease in mice. Two of the transcription factors, highly similar to activating transcription factors (ATFs), coordinate a complex secondary gene response involved in pathogenesis. The significance of our research is in characterizing the initial stages that lead to evasion of the host innate immune response and, in consequence, the dissemination of the infection. This genetic study offers possible targets for novel antifungal drugs against these opportunistic human pathogens.es
dc.language.isoenes
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 Internacional*
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 Internacional*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/*
dc.subjectInnate immunityes
dc.subjectMucormycosises
dc.subjectEmerging pathogenses
dc.titleMucor circinelloides Thrives inside the Phagosome through an Atf-Mediated Germination Pathway.es
dc.typearticlees
dc.rights.accessRightsopenAccesses
dc.description.disciplineMedicinaes
dc.identifier.doi10.1128/mBio.02765-18es


Files in this item

This item appears in the following Collection(s)

Show simple item record

Attribution-NonCommercial-NoDerivatives 4.0 Internacional
Except where otherwise noted, this item's license is described as Attribution-NonCommercial-NoDerivatives 4.0 Internacional