Decreased expression of 14-3-3 in<i>Paracoccidioides brasiliensis</i>confirms its involvement in fungal pathogenesis

Marcos, Caroline Maria; Silva, Julhiany de Fátima da; Oliveira, Haroldo César de; Assato, Patrícia Akemi; Singulani, Júnya de Lacorte; López, Annika; Tamayo, Diana; Hernández, Orville; McEwen, Juan G.; Mendes-Giannini, María José Soares; Fusco‐Almeida, Ana Marisa

doi:10.1080/21505594.2015.1122166

Cited by 28 publications

(31 citation statements)

References 91 publications

(72 reference statements)

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“…Importantly, the virulence of 14-3-3 siRNA treated Paracoccidioides yeast cells was significantly attenuated in a Galleria mellonella model of infection. 17 Together these results indicate that Pb14-3-3 plays a major role not only in Paracoccidioides virulence, but also in the morphological program of this fungus. Morphological changes during interaction with the host are critical for the pathogenicity of different fungi, such as Candida albicans (yeast to hyphal growth), 19 H. capsulatum (mycelium to yeast) 20 and Cryptococcus neoformans (capsule enlargement and titan cell formation).…”

Section: Marcos Et Almentioning

confidence: 61%

“…Pb14-3-3 silenced cells were unable to undergo either yeast-to-mycelium or mycelium-to-yeast transitions, which is particularly significant as the parasitic form (yeast form) is more resistant to killing by host effector cells>. 17 Additionally, the 14-3-3 silenced Paracoccidoides cells were smaller and produced lower numbers of buds compared to untreated yeast cells. Importantly, the virulence of 14-3-3 siRNA treated Paracoccidioides yeast cells was significantly attenuated in a Galleria mellonella model of infection.…”

Section: Marcos Et Almentioning

confidence: 99%

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Effects of silencing 14-3-3 protein in Paracoccidiodes brasiliensis infection

García-Rodas

Nosanchuk

2016

Virulence

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Section: Marcos Et Almentioning

confidence: 61%

Section: Marcos Et Almentioning

confidence: 99%

Effects of silencing 14-3-3 protein in Paracoccidiodes brasiliensis infection

García-Rodas

Nosanchuk

2016

Virulence

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“…It also acts as an immunomodulatory agent [44, 45]. Yeast transformation was mediated by ATMT [23, 46], a system reported to be successful when employed to obtain P. brasiliensis knocked-down clones for proteins playing relevant roles in the fungal virulence or pathogenesis, e.g., CDC42 [17], PbHAD32 [24], asSconC [16], PbGP43 [26], PbP27 [27], Pb14-3-3 [28], and PbSOD3 [29]. By applying the ATMT methodology, we recently obtained PCN-knocked-down P. brasiliensis yeasts, which made possible identifying PCN as a fungal virulence factor [18].…”

Section: Discussionmentioning

confidence: 99%

“…The publication of the complete genome sequence of three isolates (Pb18, Pb03, and Pb01) from the Paracoccidioides genus [30, 31] allowed further knowledge on genome of these species opening new targets for study. In recent studies [28, 29], strains with downregulation of Pb14-3-3 and PbSOD3 genes were developed by using aRNA through ATMT technology. It was shown that the Pb14-3-3 contributes for the fungal attachment to ECM/pneumocytes and fungal virulence [28], whereas PbSOD3 is essential for events underlying host-pathogen interaction [29].…”

Section: Introductionmentioning

confidence: 99%

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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

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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 ...

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14-3-3 proteins are involved in growth, hyphal branching, ganoderic acid biosynthesis, and response to abiotic stress in Ganoderma lucidum

Zhang

Shi

Chen

et al. 2018

Appl Microbiol Biotechnol

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Ganoderma lucidum, which contains many pharmacologically active compounds, is regarded as a traditional medicinal fungus. Nevertheless, the scarcity of basic research limits the commercial value and utilization of G. lucidum. As a class of highly conserved, phosphopeptide-binding proteins present in all eukaryotes, 14-3-3 proteins play vital roles in controlling multiple physiological processes, including signal transduction, primary metabolism, and stress responses. However, knowledge of the roles of 14-3-3 proteins in Basidiomycetes is sparse. In this article, two homologs of 14-3-3 proteins, encoded by the two distinct genes GlBmh1 and GlBmh2, were distinguished in G. lucidum. We found that GlBmh1 and GlBmh2 were expressed at various developmental stages, including in vegetative mycelium cultivated on solid medium and in primordia and fruiting bodies. Moreover, we constructed GlBmh1 single-silenced strains, GlBmh2 single-silenced strains, and 14-3-3 double-silenced mutants for further study. When GlBmh1 and GlBmh2 were inhibited by RNA interference, the growth rate of mycelia was decreased, and the distance between the aerial hyphal branches was reduced; responses to various abiotic stresses such as oxidants and cell wall and osmotic stressors were also changed. Furthermore, the contents of secondary metabolite ganoderic acids (GAs) were increased after GlBmh1 and GlBmh2 were simultaneously silenced. Taken together, we provide evidence that implicates potential roles for the two 14-3-3 proteins in affecting growth and GA biosynthesis, thereby providing new insights into the basic functions of 14-3-3 proteins in G. lucidum.

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Decreased expression of 14-3-3 inParacoccidioides brasiliensisconfirms its involvement in fungal pathogenesis

Cited by 28 publications

References 91 publications

Effects of silencing 14-3-3 protein in Paracoccidiodes brasiliensis infection

Effects of silencing 14-3-3 protein in Paracoccidiodes brasiliensis infection

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

14-3-3 proteins are involved in growth, hyphal branching, ganoderic acid biosynthesis, and response to abiotic stress in Ganoderma lucidum

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