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

Abstract

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.

Antifungal and antioxidant activity of fatty acid methyl esters from vegetable oils

“…Moreover, FAMEs (soybean, corn and sunflower) showed better activity than SMX-THT (P = 0.0001) against the isolates of P. brasiliensis Pb-18, Pb-608, Pb-1017, Pb-9673 and P. lutzii 01. SMX-THT is used in the treatment of PCM, mainly in endemic regions where other therapy (such as itraconazole) is not easily available; consequently, therapy consisting of SMX-THT is a useful option (de Oliveira et al 2015, Shikanai-Yasuda 2015. The difference in antifungal activity between different FAMEs, against 11 isolates of Paracoccidioides spp., is not statistically significant (P < 0.05).…”

“…The main disadvantage of SMX-THT is the need for long-term treatment (more than 12 months) in moderate and severe cases which can lead patients to abandon treatment (Brummer et al 1993, Paniago et al 2003, Travassos et al 2008. Amphotericin B therapy is the best choice for severe cases of PCM, but toxicity, mainly nephrotoxicity, is related to this drug which will sometimes require discontinuation of this therapy (de Oliveira et al 2015, Ferreira 2009, ShikanaiYasuda 2015. Relapses, a common event in PCM patients, associated with toxicity represent an unresolved problem in the conventional therapeutic approach (Travassos et al 2008, Travassos andTaborda 2012).…”

Fungal communities (Mycobiome) as potential ecological indicators within confluence stretch of Ganges and Yamuna Rivers, India

“…Furthermore, a higher relative abundance of uncommon opportunistic yeasts such as Kluveromyces, Lodderomyces, Clavispora, Meyerozyma, Yarrowia and Malassezia , previously isolated from bloodstream infections was also noted in this study (Lockhart et al 2008; Taj-Aldeen et al 2014; Cebeci Güler et al 2017). Besides, other opportunistic group of fungal pathogens such as Coccidioides, Paracoccidioides, Aspergillus, Penicillium responsible for respiratory tract infections and onchomycosis were also detected (Vélez and Díaz 2004; Montes et al 2015). Occurrence of these opportunistic fungi could be correlated with the epidemiological data of water-borne diseases acquired by the bathers after the mass bathing event of Kumbh mela taking place every 6 or 12 years at the confluence of River Ganges and River Yamuna (Tyagi et al 2013), while the existence of bio-indicator species of pollution could be correlated with the massive anthropic inputs in these rivers (Misra and Misra 2010; Zhang et al 2018).…”

Paracoccidioides spp. catalases and their role in antioxidant defense against host defense responses

“…Dimorphic fungal pathogens are equipped with a strong antioxidant defense system that provides them with different features and mechanisms required to efficiently establish infection and cause disease (de Oliveira et al, 2015; Perez-Nadales et al, 2014). Among these are the production of proteins that prevent host effector cells from eliciting an oxidative burst, the presence of nonenzymatic antioxidants (melanin) and the utilization of enzymatic antioxidants such as SODs and CATs, which they differentially encode and express.…”

“…They have evolved mechanisms that allow them to adapt and grow within the host and cause disease (de Oliveira et al, 2015; Perez-Nadales et al, 2014). Once inside the host, dimorphic fungi are challenged by a higher temperature that not only induces the transition to the parasitic form, but also increases the generation of Reactive Oxygen Species (ROS), as well as the oxidative damage resulting from the inhibition of the mitochondrial respiration (Martins et al, 2011; Ruiz et al, 2011; Vacca et al, 2004).…”