A hidden battle in the dirt: soil amoebae interactions with<i>Paracoccidioides</i>spp

Albuquerque, Patrícia; Nicola, André Moraes; Magnabosco, Diogo Almeida Gomes; Derengowski, Lorena da Silveira; Crisóstomo, Luana Soares; Xavier, Luciano Costa Gomes; Frazão, Stefânia de Oliveira; Guilhelmelli, Fernanda; Oliveira, Marco Antônio de; Hurtado, Fabián Andrés; Teixeira, Marcus de Melo; Guimarães, Allan J.; Paes, Hugo Costa; Bagagli, Eduardo; Felipe, Maria Sueli Soares; Casadevall, Arturo; Silva-Pereira, Ildinete

doi:10.1101/564435

Cited by 2 publications

References 45 publications

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Amoeba predation ofCryptococcus: A quantitative and population genomic evaluation of the Accidental Pathogen hypothesis

Sauters

Roth

Murray

et al. 2022

Preprint

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The "Amoeboid Predator-Fungal Animal Virulence Hypothesis" posits that interactions with environmental phagocytes shape the evolution of virulence traits in fungal pathogens. In this hypothesis, selection to avoid predation by amoeba inadvertently selects for traits that contribute to fungal escape from phagocytic immune cells. Here, we investigate this hypothesis in the human fungal pathogens Cryptococcus neoformans and Cryptococcus deneoformans. Applying quantitative trait locus (QTL) mapping and comparative genomics, we discovered a cross-species QTL region that is responsible for variation in resistance to amoeba predation. In C. neoformans, this same QTL was found to have pleiotropic effects on melanization, an established virulence factor. Through fine mapping and population genomic comparisons, we identified the gene encoding the transcription factor BZP4 that underlies this pleiotropic QTL and we show that decreased expression of this gene reduces melanization and increases susceptibility to amoeba predation. Despite the joint effects of BZP4 on amoeba resistance and melanin production, we find no relationship between BZP4 genotype and escape from macrophages or virulence in murine models of disease. Our findings provide new perspectives on how microbial ecology shapes the genetic architecture of fungal virulence, and suggests the need for more nuanced models for the evolution of pathogenesis that account for the complexities of both microbe-microbe and microbe-host interactions.

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Amoeba predation ofCryptococcus: A quantitative and population genomic evaluation of the Accidental Pathogen hypothesis

Sauters

Roth

Murray

et al. 2022

Preprint

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Transcriptional Remodeling Patterns in Murine Dendritic Cells Infected with Paracoccidioides brasiliensis: More Is Not Necessarily Better

de-Souza-Silva

Hurtado

Tavares

et al. 2020

JoF

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Most people infected with the fungus Paracoccidioides spp. do not get sick, but approximately 5% develop paracoccidioidomycosis. Understanding how host immunity determinants influence disease development could lead to novel preventative or therapeutic strategies; hence, we used two mouse strains that are resistant (A/J) or susceptible (B10.A) to P. brasiliensis to study how dendritic cells (DCs) respond to the infection. RNA sequencing analysis showed that the susceptible strain DCs remodeled their transcriptomes much more intensely than those from the resistant strain, agreeing with a previous model of more intense innate immunity response in the susceptible strain. Contrastingly, these cells also repress genes/processes involved in antigen processing and presentation, such as lysosomal activity and autophagy. After the interaction with P. brasiliensis, both DCs and macrophages from the susceptible mouse reduced the autophagy marker LC3-II recruitment to the fungal phagosome compared to the resistant strain cells, confirming this pathway’s repression. These results suggest that impairment in antigen processing and presentation processes might be partially responsible for the inefficient activation of the adaptive immune response in this model.

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A hidden battle in the dirt: soil amoebae interactions withParacoccidioidesspp

Cited by 2 publications

References 45 publications

Amoeba predation ofCryptococcus: A quantitative and population genomic evaluation of the Accidental Pathogen hypothesis

Amoeba predation ofCryptococcus: A quantitative and population genomic evaluation of the Accidental Pathogen hypothesis

Transcriptional Remodeling Patterns in Murine Dendritic Cells Infected with Paracoccidioides brasiliensis: More Is Not Necessarily Better

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