Additive Effect of rPb27 Immunization and Chemotherapy in Experimental Paracoccidioidomycosis

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

doi:10.1371/journal.pone.0017885

Cited by 29 publications

(16 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Extensive efforts have been made for all three diseases. Encouraging results have been seen recently with a DNA vaccine strategy for pneumocystis (Feng et al , 2011) and paracoccidioidomycosis (Fernandes et al , 2011). A recent study has been published regarding active vaccination for cryptococcosis (Chow & Casadevall, 2011).…”

Section: Vaccine Development For Other Fungal Pathogens Causing Haemamentioning

confidence: 99%

Fungal cell wall vaccines: an update

Edwards

2012

Journal of Medical Microbiology

View full text Add to dashboard Cite

This discussion is intended to be an overview of current advances in the development of fungal cell wall vaccines with an emphasis on Candida; it is not a comprehensive historical review of all fungal cell wall vaccines. Selected, more recent, innovative strategies for developing fungal vaccines will be highlighted. Both scientific and logistical obstacles related to the development of, and clinical use of, fungal vaccines will be discussed.

show abstract

Section: Vaccine Development For Other Fungal Pathogens Causing Haemamentioning

confidence: 99%

Fungal cell wall vaccines: an update

Edwards

2012

Journal of Medical Microbiology

View full text Add to dashboard Cite

show abstract

“…are poorly known owing to the lack of adequate characterization of fungal components. Among them, we highlight the glycoprotein gp43 [6-10], Hsp60 [11-13], Pb40 [14], Pb27 [15], SconCp [16], Cdc42p [17] and paracoccin (PCN) [18-20]. We described PCN from P. brasiliensis as a major protein component of a GlcNAc-binding fraction of yeast extracts [19, 20].…”

Section: Introductionmentioning

confidence: 99%

Paracoccin overexpression in Paracoccidioides brasiliensis reveals the influence of chitin hydrolysis on fungal virulence and host immune response

Vcs

Ricci-Azevedo

et al. 2019

Preprint

View full text Add to dashboard Cite

30Paracoccidioides brasiliensis and P. lutzii, etiological agents of 31 paracoccidioidomycosis (PCM), develop as mycelia at 25-30 °C and as yeast at 35-37 °C. Only 32 a few Paracoccidioides spp. proteins are well characterized. Thus, we studied paracoccin 33 (PCN) from P. brasiliensis, its role in the fungus biology, and its relationship with the host 34 innate immune cells. Cloning and heterologous expression analysis revealed its lectin, 35 enzymatic, and immunomodulatory properties. Recently, we employed a system based on 36 Agrobacterium tumefaciens-mediated transformation to manipulate P. brasiliensis yeast genes 37 to obtain clones knocked-down for PCN, which after all, are unable to transit from yeast to 38 mycelium forms, causing a mild pulmonary disease. Herein, we generate P. brasiliensis 39 overexpressing PCN (ov-PCN). To date, it was not explored the overexpressing of endogenous 40 components in Paracoccidioides spp. Therefore, we investigate the role of PCN in fungal 41 biology and pathogenesis. Augmented levels of PCN mRNA and protein, and N-42 acetylglucosaminidase activity confirmed PCN overexpression in ov-PCN of P. brasiliensis 43 yeasts. Interestingly, PCN overexpression did not affect the yeasts' growth or viability and 44 favored cell separation. The ov-PCN clones transitioned faster to the mycelium form than the 45 wt-PCN yeasts. Concerning infection, while most of mice infected with the wt-yeasts (90%) 46 survive at least until the 70 th day, all mice infected with ov-PCN yeasts were already died at the 47 35 th day post-infection. In vitro assays showed that ov-PCN were more susceptible to 48 phagocytosis by macrophages. Finally, it was verified that the chitin particles isolated from the 49 ov-PCN cells were smaller than those obtained from the wt-PCN yeasts. Macrophages 50 stimulated with the chitin isolated from ov-PCN produce IL-10, whereas the particles with a 51 wider size range harvested from wt-PCN yeasts induced TNF-α and IL-1β secretion. The anti-52 inflammatory microenvironment from macrophage stimulation with small chitin particles 53 hampers the development of a protective immune response against the fungus. We postulated 3 54 that the high grade of chitin cleavage, as the results of augmented PCN expression, favors 55 pathogenesis following P. brasiliensis infection. Thus, PCN is a relevant virulence fungal 56 factor. 57 58 AUTHOR SUMMARY 59 Paracoccidioides spp. are pathogenic fungi that cause paracoccidioidomycosis (PCM) 60 in humans, the main deep mycosis of Latin America. Recently, by knocking down the 61 paracoccin gene, our group showed that this lectin is necessary for the morphological transition 62 from yeast to hyphae, and that this decrease results in low P. brasiliensis virulence. Here, after 63 overexpress PCN, we revealed the importance of the yeast chitin hydrolysis to the host 64 response. Infection of mice with ov-PCN yeasts causes severe lung disease compared to 65 moderate disease caused by wt-PCN yeasts. The release of smaller chitin particles ...

show abstract

“…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

View full text Add to dashboard Cite

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.

show abstract

Additive Effect of rPb27 Immunization and Chemotherapy in Experimental Paracoccidioidomycosis

Cited by 29 publications

References 28 publications

Fungal cell wall vaccines: an update

Fungal cell wall vaccines: an update

Paracoccin overexpression in Paracoccidioides brasiliensis reveals the influence of chitin hydrolysis on fungal virulence and host immune response

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

Contact Info

Product

Resources

About