Insights Into Histoplasma capsulatum Behavior on Zinc Deprivation.

Leandro Do Prado Assunção,Mirelle Garcia Silva-Bailão,Sônia Nair Báo,Lilian Cristiane Baeza,Janaina Gomes De Siqueira,Alexandre Melo Bailão,Dayane Moraes,Lucas Weba Soares,Célia Maria De Almeida Soares

doi:10.3389/fcimb.2020.573097

Leandro Do Prado Assunção, Mirelle Garcia Silva-Bailão + Show 7 more

Open Access

https://doi.org/10.3389/fcimb.2020.573097

Copy DOI

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.

Highlights

H. capsultatum is a thermal dimorphic fungus that causes histoplasmosis, a mycosis with worldwide incidence and prevalence in temperate and tropical climates (Aide, 2009)
Sequences of zinc homeostasis proteins of A. fumigatus, C. neoformans, P. brasiliensis, and S. cerevisiae were used as templates
Since zinc limitation is one of the GM-CSF-activated macrophage strategies to control H. capsulatum infection (Vignesh et al, 2013), fungal growth was assessed in a zinclimited environment

Summary

Introduction

H. capsultatum is a thermal dimorphic fungus that causes histoplasmosis, a mycosis with worldwide incidence and prevalence in temperate and tropical climates (Aide, 2009). This disease is widely distributed in Central and North America, mainly in the United States, Panama, and Honduras. Fungal yeasts are capable to infect and survive in phagocytic cells, including alveolar macrophages, polymorphonuclear leukocytes, and dendritic cells (De Sanchez and Carbonell, 1975; Schaffner et al, 1986; Gildea et al, 2001). Zinc deprivation has been identified as a microbicidal strategy used by host cells to control H. capsulatum infection (Garfoot and Rappleye, 2016; Shen and Rappleye, 2017)

Methods

Results

Discussion

Conclusion