The combined use of Paracoccidioides brasiliensis Pb40 and Pb27 recombinant proteins enhances chemotherapy effects in experimental paracoccidioidomycosis

Fernandes, Viviane Cristina; Martins, Estefânia M.N.; Boeloni, Jankerle Neves; Coitinho, Juliana Barbosa; Serákides, Rogéria; Góes, Alfredo M.

doi:10.1016/j.micinf.2011.06.004

Cited by 18 publications

(12 citation statements)

References 49 publications

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“…brasiliensis is under investigation for its use in the prophylaxis and treatment of PCM [18]. The rPb27 and rPb40, in addition to fluconazole chemotherapy, showed an additive protective effect [19, 20]. Moreover, the P .…”

Section: Introductionmentioning

confidence: 99%

Detrimental Effect of Fungal 60-kDa Heat Shock Protein on Experimental Paracoccidioides brasiliensis Infection

et al. 2016

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The genus Paracoccidioides comprises species of dimorphic fungi that cause paracoccidioidomycosis (PCM), a systemic disease prevalent in Latin America. Here, we investigated whether administration of native 60-kDa heat shock protein of P. brasiliensis (nPbHsp60) or its recombinant counterpart (rPbHsp60) affected the course of experimental PCM. Mice were subcutaneously injected with nPbHsp60 or rPbHsp60 emulsified in complete’s Freund Adjuvant (CFA) at three weeks after intravenous injection of P. brasiliensis yeasts. Infected control mice were injected with CFA or isotonic saline solution alone. Thirty days after the nPbHsp60 or rPbHsp60 administration, mice showed remarkably increased fungal load, tissue inflammation, and granulomas in the lungs, liver, and spleen compared with control mice. Further, rPbHsp60 treatment (i) decreased the known protective effect of CFA against PCM and (ii) increased the concentrations of IL-17, TNF-α, IL-12, IFN-γ, IL-4, IL-10, and TGF-β in the lungs. Together, our results indicated that PbHsp60 induced a harmful immune response, exacerbated inflammation, and promoted fungal dissemination. Therefore, we propose that PbHsp60 contributes to the fungal pathogenesis.

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Section: Introductionmentioning

confidence: 99%

Detrimental Effect of Fungal 60-kDa Heat Shock Protein on Experimental Paracoccidioides brasiliensis Infection

et al. 2016

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“…Studies with yeast cells of P. brasiliensis, attenuated by gamma irradiation (LevRad), have been providing promising results. These yeast cells may promote a higher protection when used as a preventive vaccine, against PCM [18,19]. There are several examples of highly effective vaccines derived from live attenuated infectious agents (mainly viruses), such as, polio, measles, mumps, rubella, varicella, influenza and rotavirus [29].…”

Section: Discussionmentioning

confidence: 99%

“…There are some reports describing the role of antigens inducing immune responses against P. brasiliensis such as soluble antigen, purified antigen, peptide, DNA vaccine and the use of attenuated yeast cells [8][9][10][11][12][13][14][15][16][17][18][19][20][21][22].…”

Section: Introductionmentioning

confidence: 99%

Evaluation of the Therapeutic Effect of Radioattenuated Yeast Cells in Experimental Paracoccidioidomycosis

Martins¹,

Fern²,

es³

et al. 2014

J Vaccines Vaccin

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Paracoccidioides brasiliensis is the agent of paracoccidioidomycosis (PCM), the most prevalent deep mycosis in Latin America. The treatment varies according to the chemotherapeutic drug and the disease severity, and the lack of it can results in high frequency of relapse and sequels. Thus, the search for new therapeutic alternatives is necessary. The aim of this study was to evaluate the therapeutic effect of P. brasiliensis yeast cells attenuated by gamma irradiation (LevRad) in Balb/c mice. Mice immunized with LevRad and/or treated with fluconazole presented a significant decrease in the CFU recovery from the lung, liver and spleen in comparison with non-immunized and non-treated infected mice (60 and 120 days after infection). After 120 days from fungal inoculation, no fungi colonies were obtained from the organs of treated and immunized mice. The tissue structure of these organs was largely preserved. At the same time, anti-Mexo specific IgG antibodies levels and TGF-β, IFN-γ, iNOS transcript levels were high and a decrease on the IL-4, IL-10 and TNF-α transcript levels was also verified. An additive protective effect of immunization with LevRad associated to chemotherapy in a PCM experimental model was verified, providing evidence of the therapeutic effect of attenuated yeast for fungal infections.

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“…Immunization with rPb27 in the presence of Propionibacterium acnes and aluminium hydroxide prior to intravenous infection by the orbital plexus with virulent P. brasiliensis (Pb18) was able to protect BALB/c mice against infection. Recently other recombinant protein, rPb40, was used associated with fluconazole and shown to reduce the fungal burden in lungs of BALB/c mice [55], [56]. Vaccination with recombinant Hsp60 also protected BALB/c mice against a lethal challenge with P. brasiliensis yeasts by stimulating cellular immune response rich in IL-12 and IFN-γ.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of PbGP43 Expression May Suggest that gp43 is a Virulence Factor in Paracoccidioides brasiliensis

et al. 2013

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Glycoprotein gp43 is an immunodominant diagnostic antigen for paracoccidioidomycosis caused by Paracoccidioides brasiliensis. It is abundantly secreted in isolates such as Pb339. It is structurally related to beta-1,3-exoglucanases, however inactive. Its function in fungal biology is unknown, but it elicits humoral, innate and protective cellular immune responses; it binds to extracellular matrix-associated proteins. In this study we applied an antisense RNA (aRNA) technology and Agrobacterium tumefaciens-mediated transformation to generate mitotically stable PbGP43 mutants (PbGP43 aRNA) derived from wild type Pb339 to study its role in P. brasiliensis biology and during infection. Control PbEV was transformed with empty vector. Growth curve, cell vitality and morphology of PbGP43 aRNA mutants were indistinguishable from those of controls. PbGP43 expression was reduced 80–85% in mutants 1 and 2, as determined by real time PCR, correlating with a massive decrease in gp43 expression. This was shown by immunoblotting of culture supernatants revealed with anti-gp43 mouse monoclonal and rabbit polyclonal antibodies, and also by affinity-ligand assays of extracellular molecules with laminin and fibronectin. In vitro, there was significantly increased TNF-α production and reduced yeast recovery when PbGP43 aRNA1 was exposed to IFN-γ-stimulated macrophages, suggesting reduced binding/uptake and/or increased killing. In vivo, fungal burden in lungs of BALB/c mice infected with silenced mutant was negligible and associated with decreased lung ΙΛ−10 and IL-6. Therefore, our results correlated low gp43 expression with lower pathogenicity in mice, but that will be definitely proven when PbGP43 knockouts become available. This is the first study of gp43 using genetically modified P. brasiliensis.

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The combined use of Paracoccidioides brasiliensis Pb40 and Pb27 recombinant proteins enhances chemotherapy effects in experimental paracoccidioidomycosis

Cited by 18 publications

References 49 publications

Detrimental Effect of Fungal 60-kDa Heat Shock Protein on Experimental Paracoccidioides brasiliensis Infection

Detrimental Effect of Fungal 60-kDa Heat Shock Protein on Experimental Paracoccidioides brasiliensis Infection

Evaluation of the Therapeutic Effect of Radioattenuated Yeast Cells in Experimental Paracoccidioidomycosis

Inhibition of PbGP43 Expression May Suggest that gp43 is a Virulence Factor in Paracoccidioides brasiliensis

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