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Published on: September 20, 2024
Insights Into Histoplasma capsulatum Behavior on Zinc Deprivation
Leandro do Prado Assunção1, Dayane Moraes1, Lucas Weba Soares1
1Molecular Biology and Biochemistry Laboratory, Institute of Biological Sciences II, Federal University of Goias (UFG), Goiania, Brazil.
Abstract:
Histoplasma capsulatum is a thermodimorphic fungus that causes histoplasmosis, a mycosis of global incidence. The disease is prevalent in temperate and tropical regions such as North America, South America, Europe, and Asia. It is known that during infection macrophages restrict Zn availability to H. capsulatum as a microbicidal mechanism. In this way the present work aimed to study the response of H. capsulatum to zinc deprivation. In silico analyses showed that H. capsulatum has eight genes related to zinc homeostasis ranging from transcription factors to CDF and ZIP family transporters. The transcriptional levels of ZAP1, ZRT1, and ZRT2 were induced under zinc-limiting conditions. The decrease in Zn availability increases fungicidal macrophage activity. Proteomics analysis during zinc deprivation at 24 and 48 h showed 265 proteins differentially expressed at 24 h and 68 at 48 h. Proteins related to energy production pathways, oxidative stress, and cell wall remodeling were regulated. The data also suggested that low metal availability increases the chitin and glycan content in fungal cell wall that results in smoother cell surface. Metal restriction also induces oxidative stress triggered, at least in part, by reduction in pyridoxin synthesis.
Insights
Histoplasma capsulatum responds to zinc deprivation by altering gene expression and protein production, impacting its cell wall and increasing susceptibility to macrophage killing. This study reveals fungal adaptations to nutrient scarcity during infection.
Area of Science:
- Mycology
- Infectious Diseases
- Molecular Biology
Background:
- Histoplasma capsulatum causes histoplasmosis, a globally prevalent fungal infection.
- Macrophages limit zinc availability to Histoplasma capsulatum as a defense mechanism.
Purpose of the Study:
- To investigate the response of Histoplasma capsulatum to zinc deprivation.
- To identify genes and proteins involved in zinc homeostasis and adaptation.
Main Methods:
- In silico analysis of zinc homeostasis genes.
- Transcriptional analysis of ZAP1, ZRT1, and ZRT2.
- Proteomics analysis at 24 and 48 hours of zinc deprivation.
Main Results:
- Eight genes related to zinc homeostasis were identified.
- Upregulation of ZAP1, ZRT1, and ZRT2 under zinc-limiting conditions.
- Differential expression of 265 proteins at 24h and 68 proteins at 48h, including those involved in energy, oxidative stress, and cell wall remodeling.
- Increased chitin and glycan content in the cell wall, leading to a smoother surface.
- Induction of oxidative stress, partly due to reduced pyridoxine synthesis.
Conclusions:
- Histoplasma capsulatum exhibits significant molecular and cellular adaptations to zinc-limiting conditions.
- These adaptations, including cell wall changes and oxidative stress, may influence fungal survival and host-pathogen interactions.
- Understanding these responses can inform strategies against histoplasmosis.
