Abstract

BackgroundParacoccidioidomycosis (PCM) is a systemic mycosis commonly found in Latin America that is caused by distinct species of Paracoccidioides genus: Paracoccidioides brasiliensis complex (S1, PS2, PS3 and PS4) and Paracoccidioides lutzii. Its pathobiology has been recently explored by different approaches to clarify the mechanisms of host-pathogen interactions underpinning PCM. The diversity of clinical forms of this disease has been attributed to both host- and fungus-related factors.Methodology/Principal findingsFor better understanding of the molecular underpinnings of host-fungus interactions, we evaluated in vivo virulence of nine Paracoccidioides brasiliensis complex isolates and correlated it to protein expression profiles obtained by two-dimensional gel electrophoresis. Based on the recovery of viable fungi from mouse organs, the isolates were classified as those having low, moderate, or high virulence. Highly virulent isolates overexpressed proteins related to adhesion process and stress response, probably indicating important roles of those fungal proteins in regulating the colonization capacity, survival, and ability to escape host immune system reaction. Moreover, highly virulent isolates exhibited enhanced expression of glycolytic pathway enzymes concomitantly with repressed expression of succinyl-CoA ligase beta chain, a protein related to the tricarboxylic acid cycle.Conclusions/SignificanceOur findings may point to the mechanisms used by highly virulent P. brasiliensis isolates to withstand host immune reactions and to adapt to transient iron availability as strategies to survive and overcome stress conditions inside the host.

Highlights

  • Paracoccidioidomycosis (PCM) is the most frequent endemic systemic mycosis in Latin America with high incidence in Brazil, Argentina, Colombia, and Venezuela [1, 2]

  • For better understanding of the molecular underpinnings of host-fungus interactions, we evaluated in vivo virulence of nine Paracoccidioides brasiliensis complex isolates and correlated it to protein expression profiles obtained by two-dimensional gel electrophoresis

  • A recent speciation event is assumed for species embedded in the P. brasiliensis complex, whereas it seems that P. brasiliensis sensu lato (s.l.) and P. lutzii are reproductively isolated in nature [6]

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Summary

Introduction

Paracoccidioidomycosis (PCM) is the most frequent endemic systemic mycosis in Latin America with high incidence in Brazil, Argentina, Colombia, and Venezuela [1, 2]. It is caused by the thermally dimorphic species of the genus Paracoccidioides. Str.), formerly known as S1, is the most widely distributed agent of PCM, occurring in Brazil, Argentina, Paraguay, Uruguay, Peru and Venezuela [6]. Paracoccidioidomycosis (PCM) is a systemic mycosis commonly found in Latin America that is caused by distinct species of Paracoccidioides genus: Paracoccidioides brasiliensis complex (S1, PS2, PS3 and PS4) and Paracoccidioides lutzii. The diversity of clinical forms of this disease has been attributed to both host- and fungus-related factors

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