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Fonsecaea pedrosoi response to zinc deprivation

ABSTRACT: Fungal diseases significantly impact human mortality and morbidity. However, despite the number of annual deaths caused by fungi exceeding 1.6 million, these microorganisms are often neglected. Fonsecaea pedrosoi is the main etiologic agent of chromoblastomycosis (CBM), a chronic mycosis that affects the skin and subcutaneous tissue that, in 2017, was included in the WHO list of neglected tropical diseases. It is essentially an occupational disease that affects individuals in poverty, causing significant morbidity and mortality. CBM is a disease of global distribution, and most cases are described in tropical and subtropical regions of America, Africa and Asia. Despite its importance in the etiology of the disease, the molecular mechanisms involved in the interaction of F. pedrosoi with the host are still poorly explored. During the infectious process, the host limits the availability of zinc to fungal pathogens in order to contain the infection, a process called nutritional immunity. In this work, we show that F. pedrosoi is able to grow in a wide range of zinc concentration and that genes related to zinc uptake are induced in zinc-limiting conditions. Proteomic analysis revealed that after 48 h of exposure to zinc scarcity synthesis of fatty acid and the pentose-phosphate pathway are up-regulated. On the other hand, protein synthesis is repressed. Additionally, glucan increases while chitin content is reduced in the cell wall under zinc limitation, demonstrating that cell wall remodeling is important for adaptation to this stress condition.

INSTRUMENT(S): Synapt MS

ORGANISM(S): Fonsecaea Pedrosoi Cbs 271.37

TISSUE(S): Conidium

SUBMITTER: Celia Soares

LAB HEAD: HPLC MS/MS UFG

PROVIDER: PXD048714 | Pride | 2024-01-29

REPOSITORIES: Pride

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			Action	DRS
	20220722_MillenaMirelle_FpZinco_R1_F1_IA_final_protein.csv	Csv
	20220722_MillenaMirelle_FpZinco_R2_F1_IA_final_protein.csv	Csv
	20220722_MillenaMirelle_FpZinco_R3_F1_IA_final_protein.csv	Csv
	20220724_MillenaMirelle_FpDTPA_R1_F1_IA_final_protein.csv	Csv
	20220724_MillenaMirelle_FpDTPA_R2_F1_IA_final_protein.csv	Csv

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Project description:Purpose: A common theme across multiple fungal pathogens is their ability to impair the establishment of a protective immune response. Although early inflammation is beneficial in containing the infection, an uncontrolled inflammatory response is detrimental and may eventually oppose disease eradication. Chromoblastomycosis (CBM), a cutaneous and subcutaneous mycosis, caused by dematiaceous fungi, is capable of inducing a chronic inflammatory response. This work was performed in order to understand how fungal cells were able to induce intense inflammatory response in the host. Methods:Peritoneal macrophages (PM) were infected for 6h with F. pedrosoi conidia or muriform cells and then lysed so that total RNA was extracted with the RNeasy kit (Qiagen). Paired-end cDNA reads (100bp) were generated using the HiSeq 2000 Sequencing system (Illumina) located at the Scripps DNA Sequencing Facility (California, USA). Quality check of the paired-end reads was performed using FASTQC, and clipping and trimming was done using CUTADAPT and PRINSEQ softwares, respectively. The filtered reads were aligned to the mouse genome downloaded from the Ensembl database using open source TopHat 2.0.9. The aligned files were ordered and indexed using Samtools followed by read count using HTSeq-count. Statistical analysis was done using the R environment for statistical computing. Gene model quantification were performed using the Bioconductor package EdgeR. Results: High throughput RNA sequencing analysis (RNA-Seq) showed a strong up-regulation of genes related to fungal recognition, cell migration, inflammation, apoptosis and phagocytosis in macrophages exposed in vitro to Fonsecaea pedrosoi muriform cells, but not F. pedrosoi conidia. This is the main fungal form responsible for the intense inflammatory pattern observed in CBM, clarifying the chronic inflammatory reaction observed in most patients. Conclusions: Our findings reveal two different fungal-host interaction strategies according to fungal form, highlighting fungal dimorphism as an important key in understanding the bipolar nature of inflammatory response in fungal infections

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Fonsecaea pedrosoi response to zinc deprivation

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