Importance of adhesins in virulence of Paracoccidioides spp.

Abstract

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.

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

“…brasiliensis uses a sequence of different mechanisms to establish successful infections, beginning with the first contact with host cells and extending through the later stages of disease. 48,49 The reduced initial adhesion observed in this study suggests that the Pb14-3-3 gene products strongly influence the initial adhesion, as reported by Andreotti et al, 2005, 27 Da Silva et al, 2013 28 and De Oliveira et al, 2015, 50 but the requirement for these proteins was bypassed following extended contact with the host cell.…”

Peptides Derived from a Phage Display Library Inhibit Adhesion and Protect the Host against Infection by Paracoccidioides brasiliensis and Paracoccidioides lutzii

“…This type of therapy is known as anti-adhesion therapy and can be an effective way to improve the efficacy of PCM treatments. In support of this idea, de Oliveira et al (2015) demonstrated that when blocking two important Paracoccidioides spp. adhesins, enolase and 14-3-3, using specifics antibodies, host organisms were able to resist fungal infection and showed increased survival.…”

“…The pathogen’s ability to colonize and invade the host tissue is strictly dependent on these proteins and the adhesion capacity of the fungus. de Oliveira et al (2015), using in vivo animal models, demonstrated that the ability to express adhesins and adhere to the host are decisive factors in the virulence of different Paracoccidioides spp. isolates.…”

New insights into a complex fungal pathogen: the case of Paracoccidioides spp.

“…This adherence mechanism is mediated by molecules, named adhesins, present on the fungal surface that allow it not only to adhere but also to invade the host tissues, contributing to development of the mycosis. Thus, several adhesins have been reported, including the 14–3–3 protein enolase, triose phosphate isomerase (TPI), glyceraldehyde 3‐phosphate dehydrogenase (GAPDH), the glycoprotein Gp43 (the main immunodominant antigen) and a hydrolase (HAD32) (de Oliveira et al ., ; Pereira et al ., ; Barbosa et al ., ; Torres et al ., ; Mendes‐Giannini et al ., ; Hernández et al ., ). Moreover, the 14–3–3 protein and Gp43 induce apoptosis in human pneumocytes (Silva et al ., ).…”