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High copper promotes cell wall remodeling and oxidative stress in Histoplasma capsulatum, as revealed by proteomics. | LitMetric

High copper promotes cell wall remodeling and oxidative stress in Histoplasma capsulatum, as revealed by proteomics.

Fungal Biol

Laboratório de Biologia Molecular (LBM), Instituto de Ciências Biológicas (ICB), Universidade Federal de Goiás (UFG), Goiânia, GO, Brazil. Electronic address:

Published: December 2023

AI Article Synopsis

  • Histoplasma, a fungal pathogen, faces nutrient stress during infection as immune cells manipulate essential nutrients, particularly metals, affecting its survival and virulence.
  • The study focused on how Histoplasma capsulatum adapts to excess copper using proteomics, revealing that while carbohydrate breakdown was suppressed, pathways for lipid degradation were activated, indicating a shift in metabolism.
  • Key findings include enhanced surface exposure of glycan and chitin, increased antioxidant enzyme production to combat oxidative stress, and elevated aerobic respiration for energy, highlighting the fungus's strategies to survive in high copper conditions.

Article Abstract

Histoplasma experiences nutritional stress during infection as a result of immune cells manipulating essential nutrients, such as metal ions, carbon, nitrogen, and vitamins. Copper (Cu) is an essential metallic micronutrient for living organisms; however, it is toxic in excess. Microbial pathogens must resist copper toxicity to survive. In the case of Histoplasma, virulence is supported by high-affinity copper uptake during late infection, and copper detoxification machinery during early macrophage infection. The objective of this study was to characterize the global molecular adaptation of Histoplasma capsulatum to copper excess using proteomics. Proteomic data revealed that carbohydrate breakdown was repressed, while the lipid degradation pathways were induced. Surprisingly, the production of fatty acids/lipids was also observed, which is likely a result of Cu-mediated damage to lipids. Additionally, the data showed that the fungus increased the exposition of glycan and chitin on the cell surface in high copper. Yeast upregulated antioxidant enzymes to counteract ROS accumulation. The induction of amino acid degradation, fatty acid oxidation, citric acid cycle, and oxidative phosphorylation suggest an increase in aerobic respiration for energy generation. Thus, H. capsulatum's adaptive response to high Cu is putatively composed of metabolic changes to support lipid and cell wall remodeling and fight oxidative stress.

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Source
http://dx.doi.org/10.1016/j.funbio.2023.05.004DOI Listing

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