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Mandel, A.

Publications and source records attributed to Mandel, A..

2 recordsLinked to original sources

Autophagy restricts fungal accommodation in the roots ofArabidopsis thaliana

Endophytic colonization of Arabidopsis thaliana by the beneficial root endophyte Serendipita indica is characterized by an initial biotrophic phase followed by a restricted host cell death-associated phase. This latter phase involves regulated cell death (RCD) for fungal accommodation. However, the host molecular pathways that limit S. indica colonization and govern symbiosis remain largely unknown. Our study demonstrates that autophagy, a major cellular degradation pathway, is activated during S. indica colonization and is required to restrict fungal colonization in Arabidopsis. Independent Arabidopsis knockout (KO) mutants deficient in autophagosome formation are more susceptible to deoxyadenosine (dAdo), a cell death inducer produced by two secreted S. indica effectors at the onset of the cell death-associated phase. In the atg5 autophagy mutant background, impaired dAdo uptake prevents dAdo-induced and symbiosis-mediated cell death. Based on our data, we propose that autophagy-mediated pro-survival responses in the host are crucial for maintaining a balanced symbiotic interaction between S. indica and Arabidopsis. In a NutshellOur study reveals that during colonization of Arabidopsis thaliana roots by the beneficial root endophyte Serendipita indica, autophagy, a key cellular degradation pathway, is activated to limit fungal colonization. Autophagy-deficient Arabidopsis mutants are more susceptible to deoxyadenosine (dAdo), a cell death inducer produced by S. indica. We propose that autophagy-mediated pro-survival responses are essential for maintaining a balanced symbiotic interaction between S. indica and Arabidopsis.

microbiology↗

The WOPR family protein Ryp1 is a key regulator of gene expression, development, and virulence in the thermally dimorphic fungal pathogen Coccidioides posadasii

Coccidioides spp. are mammalian fungal pathogens endemic to the southwestern US and other desert regions of Mexico, central and South America, with the bulk of US infections occurring in California and Arizona. In the soil, Coccidioides grows in a hyphal form that differentiates into 3-5 micron asexual spores (arthroconidia). When arthroconidia are inhaled by mammals they undergo a unique developmental transition from polar hyphal growth to isotropic expansion with multiple rounds of nuclear division, prior to segmentation, forming large spherules filled with endospores. Very little is understood about the molecular basis of spherule formation. Here we characterize the role of the conserved transcription factor Ryp1 in Coccidioides development. We show that Coccidioides {Delta}ryp1 mutants have altered colony morphology under hypha-promoting conditions and are unable to form mature spherules under spherule-promoting conditions. We analyze the transcriptional profile of wild-type and {Delta}ryp1 mutant cells under hypha- and spherule-promoting conditions, thereby defining a set of hypha- or spherule-enriched transcripts ("morphology-regulated" genes) that are dependent on Ryp1 for their expression. Forty percent of morphology-regulated expression is Ryp1-dependent, indicating that Ryp1 plays a dual role in both hyphal and spherule development. Ryp1-dependent transcripts include key virulence factors such as SOWgp, which encodes the spherule outer wall glycoprotein. Concordant with its role in spherule development, we find that the {Delta}ryp1 mutant is completely avirulent in the mouse model of coccidioidomycosis, indicating that Ryp1-dependent pathways are essential for the ability of Coccidioides to cause disease. Vaccination of C57BL/6 mice with live {Delta}ryp1 spores does not provide any protection from lethal C. posadasii intranasal infection, consistent with our findings that the {Delta}ryp1 mutant fails to make mature spherules and likely does not express key antigens required for effective vaccination. Taken together, this work identifies the first transcription factor that drives mature spherulation and virulence in Coccidioides. Author SummaryCoccidioides species, C. immitis and C. posadasii, are dimorphic fungal pathogens that commonly infect humans in North, Central, and South America, causing the respiratory fungal disease known as Valley Fever. Coccidioides grows as hyphae in the soil and differentiates into unique structures called spherules in the mammalian host. Spherules expand and internally divide to form endospores, which are released to facilitate dissemination of the pathogen within the host. The mechanisms underlying spherule differentiation remain largely unknown. In this study, we generated knockout mutants ({Delta}ryp1) of the conserved transcription factor Ryp1 in C. posadasii and characterized its role in spherule formation and virulence. We found that Ryp1 is required for the formation of mature spherules and colonization of mouse lungs. Transcriptional profiling of the {Delta}ryp1 mutant and the wild-type strain shows that Ryp1 regulates the expression of a subset of the transcripts that are either upregulated in wild-type spherules or in wild-type hyphae. These findings suggest that Ryp1 has a dual role in regulating morphology and virulence under host conditions as well as regulating genes involved in hyphal growth in the environment.

microbiology↗