Influence of the Paracoccidioides brasiliensis14-3-3 and gp43 proteins on the induction of apoptosis in A549 epithelial cells

Silva, Julhiany de Fátima da; Vicentim, Juliana; Oliveira, Haroldo César de; Marcos, Caroline Maria; Assato, Patrícia Akemi; Andreotti, Patrícia Ferrari; Silva, Juliana Leal Monteiro da; Soares, Christiane Pienna; Benard, Gil; Almeida, Ana Marisa Fusco; Mendes-Giannini, María José Soares

doi:10.1590/0074-02760150057

Cited by 18 publications

(17 citation statements)

References 50 publications

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“…Paracoccidiodes brasiliensis may modulate apoptosis of epithelial cells A549 by the expression of apoptotic molecules such as Bcl-2, Bak, and caspase-3, confirming the inducing of apoptosis by the fungus which can then survive and spread to other parts of the body ( Del Vecchio et al, 2009 ). More recently, Silva et al (2015) , showed that the 14-3-3 and gp43 adhesins has strong influence in this process. Campanelli et al (2003) demonstrated that apoptosis mediated by Fas-FasL and CTLA-4 engagement are involved in modulating the immune response in patients infected with PCM.…”

Section: Host Cells Manipulation By Paracoccidioides mentioning

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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Section: Host Cells Manipulation By Paracoccidioides mentioning

confidence: 99%

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

et al. 2015

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“…The lung is the first site of infection, but the yeast can spread to other organs. It is speculated that modulation of host cell apoptosis is advantageous for the fungi because the micro-organisms can evade the killing activity of the phagocytic antimicrobial machinery in tissues; this would prevent their death, and the fungi could disseminate through the host's circulatory system and stimulate the inflammatory response to invade tissues as a consequence of these injures [8]. There is evidence that P. brasiliensis is able to modulate the chronic inflammatory response through nitric oxide (NO), which improves tissue degradation and/or decreases extracellular matrix synthesis by controlling inflammatory and immune mediators.…”

Section: Introductionmentioning

confidence: 99%

Evaluation of the efficacy of antifungal drugs against Paracoccidioides brasiliensis and Paracoccidioides lutzii in a Galleria mellonella model

Singulani

Scorzoni

Silva

et al. 2016

International Journal of Antimicrobial Agents

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Paracoccidioides brasiliensis and P. lutzii belong to a group of thermodimorphic fungi and cause paracoccidioidomycosis (PCM), which is a human systemic mycosis endemic in South and Central America. Patients with this mycosis are commonly treated with amphotericin B (AmB) and azoles. The study of fungal virulence and the efficacy and toxicity of antifungal drugs has been successfully performed in a Galleria mellonella infection model. In this work, G. mellonella larvae were infected with two Paracoccidioides spp. and the efficacy and toxicity of AmB and itraconazole were evaluated in this model for the first time. AmB and itraconazole treatments were effective in increasing larval survival and reducing the fungal burden. The fungicidal and fungistatic effects of AmB and itraconazole, respectively, were observed in the model. Furthermore, these effects were independent of changes in haemocyte number. G. mellonella can serve as a rapid model for the screening of new antifungal compounds against Paracoccidioides and can contribute to a reduction in experimental animal numbers in the study of PCM.

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“…Mononuclear cells from patients with PCM, stimulated with gp43, presented high rates of programmed cell death (37). In A549 cells infected with Pb and treated with gp43, there was also an increase in the amount of apoptosis (40). Therefore, these results suggest that in the Pb-infected spleen, the increase in gp43 expression may have been a triggering factor for apoptosis.…”

Section: Discussionmentioning

confidence: 88%

Combination of Histopathology and FT‐Raman Spectroscopy for the Study of Experimental Paracoccidioidomycosis in the Spleen

Mansano¹,

Morais²,

Moratto³

et al. 2017

Photochem & Photobiology

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Paracoccidioides brasiliensis (Pb) can disseminate through the lymphatic and hematogenic pathways. As a result the spleen and other lymphoid organs are targets of paracoccidioidomycosis. There are few studies describing this disease in the spleen and more detailed descriptions are required. This study combines Histopathology and Fourier Transform Raman Spectroscopy (FT‐Raman) methods to study spleen infected by Pb. The Swiss mice were euthanized after 1, 2, 4 and 8 weeks of infection with Pb, and their spleens were removed for ex vivo analyzes. Histopathological evaluation revealed that the red pulp was the area most affected, presenting the highest concentration of yeasts, inflammatory cells and cells in apoptosis, with no observation of typical granuloma formation. The main physical–chemical changes were detected in the spectral ranges between 1730–1590 cm−1 and 1390–1280 cm−1 attributed to amide I and vibrational deformation mode of CH3 and CH2 molecules, respectively. The amide I was correlated to total protein content and CH3 and CH2 molecules to collagen of the spleen. The association between histological and physical–chemical methods enabled detection of several alterations in the spleen, including apoptosis, contributing to a better understanding of paracoccidioidomycosis, a tropical neglected disease.

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Influence of the Paracoccidioides brasiliensis14-3-3 and gp43 proteins on the induction of apoptosis in A549 epithelial cells

Cited by 18 publications

References 50 publications

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

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

Evaluation of the efficacy of antifungal drugs against Paracoccidioides brasiliensis and Paracoccidioides lutzii in a Galleria mellonella model

Combination of Histopathology and FT‐Raman Spectroscopy for the Study of Experimental Paracoccidioidomycosis in the Spleen

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