Proteomic Analysis of Sporothrix schenckii Exposed to Oxidative Stress Induced by Hydrogen Peroxide

Dulce O Saucedo-Campa,Ana L Martínez-Rocha,Carlos A Alba-Fierro,Estela Ruiz-Baca,Emmanuel Ríos-Castro,Mayra Cuéllar-Cruz,Miguel A Escobedo-Bretado

doi:10.3390/pathogens11020230

Dulce O Saucedo-Campa, Ana L Martínez-Rocha + Show 5 more

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https://doi.org/10.3390/pathogens11020230

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Abstract

Sporothrix schenckii modulates the expression of its cell wall proteins (CWPs) in response to reactive oxygen species (ROS) generated by the phagocytic cells of the human host, which allows it to evade and escape the immune system. In this study, we performed a comparative proteomic analysis of the CW of S. schenckii after exposure and nonexposure to H2O2. Several CWPs involved in CW remodeling and fungal pathogenesis that modulated their expression in response to this oxidizing agent were identified, as were a number of antioxidant enzymes and atypical CWPs, called moonlighting proteins, such as the Hsp70-5, lipase 1 (Lip1), enolase (Eno), and pyruvate kinase (Pk). Moreover, RT-qPCR assays demonstrated that the transcription of genes HSP70-5, LIP1, ENO, and PK is regulated in response to the oxidant. The results indicated that S. schenckii differentially expressed CWPs to confer protection against ROS upon this fungus. Furthermore, among these proteins, antioxidant enzymes and interestingly, moonlighting-like CWPs play a role in protecting the fungus from oxidative stress (OS), allowing it to infect human host cells.

Highlights

Sporotrichosis is an emergent subcutaneous mycosis that affects both humans and animals
In order to calculate the minimum lethal dose (MLD) of H2 O2 for S. schenckii, yeast cultures of the fungus in the exponential growth phase were exposed to different concentrations (0–200 mM)
In order to identify the cell wall proteins (CWPs) of S. schenckii that are differentially expressed in the oxidative stress response (OSR) induced by H2 O2, CWPs were extracted from

Summary

Introduction

Sporotrichosis is an emergent subcutaneous mycosis that affects both humans and animals. It is a cosmopolitan disease, reported to be endemic in the tropical and subtropical regions of Latin America, Africa and Asia [1,2,3]. Sporothrix schenckii, which belongs to the pathogenic clade of the genus Sporothrix, is the species most frequently associated with this disease [4]. The human body’s resistance to pathogenic fungi depends largely on the behavior of the phagocytic cells of the innate immune system, especially on that of neutrophils and macrophages. Phagocytes are very efficient at recognizing fungi, mainly by recognizing specific molecules of their cell surface known as pathogen-associated molecular pattern molecules (PAMPs) through pattern recognition receptors (PRRs). When phagocytes recognize fungal cells, they absorb and degrade them inside phagosomal compartments

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