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Propionate metabolism in a human pathogenic fungus: proteomic and biochemical analyses.
IMA Fungus. 2020; 11:9.IF

Abstract

Fungi of the complex Paracoccidioides spp. are thermodimorphic organisms that cause Paracoccidioidomycosis, one of the most prevalent mycoses in Latin America. These fungi present metabolic mechanisms that contribute to the fungal survival in host tissues. Paracoccidioides lutzii activates glycolysis and fermentation while inactivates aerobic metabolism in iron deprivation, a condition found during infection. In lungs Paracoccidioides brasiliensis face a glucose poor environment and relies on the beta-oxidation to support energy requirement. During mycelium to yeast transition P. lutzii cells up-regulate transcripts related to lipid metabolism and cell wall remodeling in order to cope with the host body temperature. Paracoccidioides spp. cells also induce transcripts/enzymes of the methylcitrate cycle (MCC), a pathway responsible for propionyl-CoA metabolism. Propionyl-CoA is a toxic compound formed during the degradation of odd-chain fatty acids, branched chain amino acids and cholesterol. Therefore, fungi require a functional MCC for full virulence and the ability to metabolize propionyl-CoA is related to the virulence traits in Paracoccidioides spp. On this way we sought to characterize the propionate metabolism in Paracoccidioides spp. The data collected showed that P. lutzii grows in propionate and activates the MCC by accumulating transcripts and proteins of methylcitrate synthase (MCS), methylcitrate dehydratase (MCD) and methylisocitrate lyase (MCL). Biochemical characterization of MCS showed that the enzyme is regulated by phosphorylation, an event not yet described. Proteomic analyses further indicate that P. lutzii yeast cells degrades lipids and amino acids to support the carbon requirement for propionate metabolism. The induction of a putative propionate kinase suggests that fungal cells use propionyl-phosphate as an intermediate in the production of toxic propionyl-CoA. Concluding, the metabolism of propionate in P. lutzii is under regulation at transcriptional and phosphorylation levels and that survival on this carbon source requires additional mechanisms other than activation of MCC.

Authors+Show Affiliations

Laboratório de Biologia Molecular, Instituto de Ciências Biológicas, Universidade Federal de Goiás, Goiânia, Brazil.Laboratório de Biologia Molecular, Instituto de Ciências Biológicas, Universidade Federal de Goiás, Goiânia, Brazil.Laboratório de Biologia Molecular, Instituto de Ciências Biológicas, Universidade Federal de Goiás, Goiânia, Brazil. Universidade Estadual de Goiás, Itapuranga, Brazil.Laboratório de Biologia Molecular, Instituto de Ciências Biológicas, Universidade Federal de Goiás, Goiânia, Brazil.Fungal Biology and Genetics Group, University of Nottingham, Nottingham, UK.Laboratório de Biologia Molecular, Instituto de Ciências Biológicas, Universidade Federal de Goiás, Goiânia, Brazil.Laboratório de Biologia Molecular, Instituto de Ciências Biológicas, Universidade Federal de Goiás, Goiânia, Brazil.Laboratório de Biologia Molecular, Instituto de Ciências Biológicas, Universidade Federal de Goiás, Goiânia, Brazil.Laboratório de Biologia Molecular, Instituto de Ciências Biológicas, Universidade Federal de Goiás, Goiânia, Brazil.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32617258

Citation

Santos, Luiz Paulo Araújo, et al. "Propionate Metabolism in a Human Pathogenic Fungus: Proteomic and Biochemical Analyses." IMA Fungus, vol. 11, 2020, p. 9.
Santos LPA, Assunção LDP, Lima PS, et al. Propionate metabolism in a human pathogenic fungus: proteomic and biochemical analyses. IMA Fungus. 2020;11:9.
Santos, L. P. A., Assunção, L. D. P., Lima, P. S., Tristão, G. B., Brock, M., Borges, C. L., Silva-Bailão, M. G., Soares, C. M. A., & Bailão, A. M. (2020). Propionate metabolism in a human pathogenic fungus: proteomic and biochemical analyses. IMA Fungus, 11, 9. https://doi.org/10.1186/s43008-020-00029-9
Santos LPA, et al. Propionate Metabolism in a Human Pathogenic Fungus: Proteomic and Biochemical Analyses. IMA Fungus. 2020;11:9. PubMed PMID: 32617258.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Propionate metabolism in a human pathogenic fungus: proteomic and biochemical analyses. AU - Santos,Luiz Paulo Araújo, AU - Assunção,Leandro do Prado, AU - Lima,Patrícia de Souza, AU - Tristão,Gabriel Brum, AU - Brock,Matthias, AU - Borges,Clayton Luiz, AU - Silva-Bailão,Mirelle Garcia, AU - Soares,Célia Maria de Almeida, AU - Bailão,Alexandre Melo, Y1 - 2020/05/05/ PY - 2019/08/27/received PY - 2020/03/11/accepted PY - 2020/7/4/entrez PY - 2020/7/4/pubmed PY - 2020/7/4/medline KW - Differential metabolism KW - Methylcitrate cycle KW - Paracoccidioides KW - Propionate kinase SP - 9 EP - 9 JF - IMA fungus JO - IMA Fungus VL - 11 N2 - Fungi of the complex Paracoccidioides spp. are thermodimorphic organisms that cause Paracoccidioidomycosis, one of the most prevalent mycoses in Latin America. These fungi present metabolic mechanisms that contribute to the fungal survival in host tissues. Paracoccidioides lutzii activates glycolysis and fermentation while inactivates aerobic metabolism in iron deprivation, a condition found during infection. In lungs Paracoccidioides brasiliensis face a glucose poor environment and relies on the beta-oxidation to support energy requirement. During mycelium to yeast transition P. lutzii cells up-regulate transcripts related to lipid metabolism and cell wall remodeling in order to cope with the host body temperature. Paracoccidioides spp. cells also induce transcripts/enzymes of the methylcitrate cycle (MCC), a pathway responsible for propionyl-CoA metabolism. Propionyl-CoA is a toxic compound formed during the degradation of odd-chain fatty acids, branched chain amino acids and cholesterol. Therefore, fungi require a functional MCC for full virulence and the ability to metabolize propionyl-CoA is related to the virulence traits in Paracoccidioides spp. On this way we sought to characterize the propionate metabolism in Paracoccidioides spp. The data collected showed that P. lutzii grows in propionate and activates the MCC by accumulating transcripts and proteins of methylcitrate synthase (MCS), methylcitrate dehydratase (MCD) and methylisocitrate lyase (MCL). Biochemical characterization of MCS showed that the enzyme is regulated by phosphorylation, an event not yet described. Proteomic analyses further indicate that P. lutzii yeast cells degrades lipids and amino acids to support the carbon requirement for propionate metabolism. The induction of a putative propionate kinase suggests that fungal cells use propionyl-phosphate as an intermediate in the production of toxic propionyl-CoA. Concluding, the metabolism of propionate in P. lutzii is under regulation at transcriptional and phosphorylation levels and that survival on this carbon source requires additional mechanisms other than activation of MCC. SN - 2210-6340 UR - https://www.unboundmedicine.com/medline/citation/32617258/Propionate_metabolism_in_a_human_pathogenic_fungus:_proteomic_and_biochemical_analyses_ DB - PRIME DP - Unbound Medicine ER -
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