Intermolecular interactions of the malate synthase of Paracoccidioides spp

Oliveira, Karine Martins de; Neto, Benedito Rodrigues da Silva; Parente, Juliana Alves; Silva, Roosevelt Alves da; Quintino, Guilherme Oliveira; Voltan, Aline Raquel; Mendes-Giannini, María José Soares; Soares, Célia Maria de Almeida; Pereira, Maristela

doi:10.1186/1471-2180-13-107

Cited by 12 publications

(12 citation statements)

References 54 publications

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“…Malate synthase has been described as an adhesin for Pb01 ( P. lutzii ) (da Silva Neto et al, 2009 ), binding to fibronectin and type I and type IV collagen. Moreover, (de Oliveira et al, 2013 ) demonstrated that Paracoccidioides malate synthase interacts with proteins of different molecular categories, such as those involved in cellular transport, protein biosynthesis, protein degradation and modification and signal transduction, suggesting that this protein plays pleiotropic roles in fungal cells. In the present study, it was expressed less during the early interaction of P. lutzii (approximately 2-fold less expression) and of P. brasiliensis (expressed approximately 1.5-fold more), but its expression was increased in both species after 1 h of interaction (approximately 4-fold for P. brasiliensis and 3-fold for P. lutzii ).…”

Section: Discussionmentioning

confidence: 99%

Importance of adhesins in virulence of Paracoccidioides spp.

et al. 2015

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Members of the Paracoccidioides genus are the etiologic agents of paracoccidioidomycosis (PCM). This genus is composed of two species: Paracoccidioides brasiliensis and Paracoccidioides lutzii. The correct molecular taxonomic classification of these fungi has created new opportunities for studying and understanding their relationships with their hosts. Paracoccidioides spp. have features that permit their growth under adverse conditions, enable them to adhere to and invade host tissues and may contribute to disease development. Cell wall proteins called adhesins facilitate adhesion and are capable of mediating fungi-host interactions during infection. This study aimed to evaluate the adhesion profile of two species of the genus Paracoccidioides, to analyze the expression of adhesin-encoding genes by real-time PCR and to relate these results to the virulence of the species, as assessed using a survival curve in mice and in Galleria mellonella after blocking the adhesins. A high level of heterogeneity was observed in adhesion and adhesin expression, showing that the 14-3-3 and enolase molecules are the most highly expressed adhesins during pathogen-host interaction. Additionally, a survival curve revealed a correlation between the adhesion rate and survival, with P. brasiliensis showing higher adhesion and adhesin expression levels and greater virulence when compared with P. lutzii. After blocking 14-3-3 and enolase adhesins, we observed modifications in the virulence of these two species, revealing the importance of these molecules during the pathogenesis of members of the Paracoccidioides genus. These results revealed new insights into the host-pathogen interaction of this genus and may enhance our understanding of different isolates that could be useful for the treatment of this mycosis.

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Section: Discussionmentioning

confidence: 99%

Importance of adhesins in virulence of Paracoccidioides spp.

et al. 2015

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“…However, besides the metabolic role, PbMLS is found in fungus cell walls and is characterized as an adhesin able to bind to fibronectin as well as types I and IV collagen ( da Silva Neto et al, 2009 ). In a study of intermolecular interactions of PbMLS, de Oliveira et al (2013) found that PbMLS present in cell walls interact with other adhesins such as enolase and TPI and this interaction could enhance the adhesion ability.…”

Section: The Adhesion Process In Pcmmentioning

confidence: 99%

Paracoccidioides-host Interaction: An Overview on Recent Advances in the Paracoccidioidomycosis

et al. 2015

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Paracoccidioides brasiliensis and P. lutzii are etiologic agents of paracoccidioidomycosis (PCM), an important endemic mycosis in Latin America. During its evolution, these fungi have developed characteristics and mechanisms that allow their growth in adverse conditions within their host through which they efficiently cause disease. This process is multi-factorial and involves host–pathogen interactions (adaptation, adhesion, and invasion), as well as fungal virulence and host immune response. In this review, we demonstrated the glycoproteins and polysaccharides network, which composes the cell wall of Paracoccidioides spp. These are important for the change of conidia or mycelial (26°C) to parasitic yeast (37°C). The morphological switch, a mechanism for the pathogen to adapt and thrive inside the host, is obligatory for the establishment of the infection and seems to be related to pathogenicity. For these fungi, one of the most important steps during the interaction with the host is the adhesion. Cell surface proteins called adhesins, responsible for the first contact with host cells, contribute to host colonization and invasion by mediating this process. These fungi also present the capacity to form biofilm and through which they may evade the host’s immune system. During infection, Paracoccidioides spp. can interact with different host cell types and has the ability to modulate the host’s adaptive and/or innate immune response. In addition, it participates and interferes in the coagulation system and phenomena like cytoskeletal rearrangement and apoptosis. In recent years, Paracoccidioides spp. have had their endemic areas expanding in correlation with the expansion of agriculture. In response, several studies were developed to understand the infection using in vitro and in vivo systems, including alternative non-mammal models. Moreover, new advances were made in treating these infections using both well-established and new antifungal agents. These included natural and/or derivate synthetic substances as well as vaccines, peptides, and anti-adhesins sera. Because of all the advances in the PCM study, this review has the objective to summarize all of the recent discoveries on Paracoccidioides-host interaction, with particular emphasis on fungi surface proteins (molecules that play a fundamental role in the adhesion and/or dissemination of the fungi to host-cells), as well as advances in the treatment of PCM with new and well-established antifungal agents and approaches.

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“…GAPDH has been intensely investigated in Paracoccidioides . It is differentially expressed in several approaches such as copper and zinc deprivation in P. lutzii (Parente et al, 2013; de Oliveira et al, 2014), up regulated in P. brasiliensis yeast cells (Rezende et al, 2011), acting as adhesin (Barbosa et al, 2006), present in the secretome of mycelia and yeast cells (Weber et al, 2012) and interacting with malate synthase (de Oliveira et al, 2013). As a moonlight macromolecule, GAPDH interacts with a large variety of proteins, forming multiprotein complexes that play unique roles within cells (Brandina et al, 2006; Ferreira et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

Interactome of Glyceraldehyde-3-Phosphate Dehydrogenase Points to the Existence of Metabolons in Paracoccidioides lutzii

et al. 2019

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Paracoccidioides is a dimorphic fungus, the causative agent of paracoccidioidomycosis. The disease is endemic within Latin America and prevalent in Brazil. The treatment is based on azoles, sulfonamides and amphotericin B. The seeking for new treatment approaches is a real necessity for neglected infections. Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is an essential glycolytic enzyme, well known for its multitude of functions within cells, therefore categorized as a moonlight protein. To our knowledge, this is the first approach performed on the Paracoccidioides genus regarding the description of PPIs having GAPDH as a target. Here, we show an overview of experimental GAPDH interactome in different phases of Paracoccidioides lutzii and an in silico analysis of 18 proteins partners. GAPDH interacted with 207 proteins in P. lutzii . Several proteins bound to GAPDH in mycelium, transition and yeast phases are common to important pathways such as glycolysis and TCA. We performed a co-immunoprecipitation assay to validate the complex formed by GAPDH with triose phosphate isomerase, enolase, isocitrate lyase and 2-methylcitrate synthase. We found GAPDH participating in complexes with proteins of specific pathways, indicating the existence of a glycolytic and a TCA metabolon in P. lutzii . GAPDH interacted with several proteins that undergoes regulation by nitrosylation. In addition, we modeled the GAPDH 3-D structure, performed molecular dynamics and molecular docking in order to identify the interacting interface between GAPDH and the interacting proteins. Despite the large number of interacting proteins, GAPDH has only four main regions of contact with interacting proteins, reflecting its ancestrality and conservation over evolution.

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Intermolecular interactions of the malate synthase of Paracoccidioides spp

Cited by 12 publications

References 54 publications

Importance of adhesins in virulence of Paracoccidioides spp.

Importance of adhesins in virulence of Paracoccidioides spp.

Paracoccidioides-host Interaction: An Overview on Recent Advances in the Paracoccidioidomycosis

Interactome of Glyceraldehyde-3-Phosphate Dehydrogenase Points to the Existence of Metabolons in Paracoccidioides lutzii

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