Paracoccidioides brasiliensis: chemical and molecular tools for research on cell walls, antifungals, diagnosis, taxonomy

Abstract

Paracoccidioides brasiliensis is a dimorphic fungus, a causative agent of paracoccidioidomycosis, one of the most frequent systemic mycoses that affect the rural population in Latin America, only geographical region in which this fungus is to be found. In this work, we discuss matters related to (a) cell wall studies based on the cloning and analysis of genes involved in the synthesis of cell wall components, and their possible roles in virulence and dimorphism in P. brasiliensis, (b) molecular taxonomy and the molecular classification of P. brasiliensis as an Ascomycete belonging in the Order Onygenales, (c) phylogeny of P. brasiliensis and the possible existence of cryptic species within the genus Paracoccidioides, and (d) new experimental antifungal drugs such as azasterols or sterol hydrazones, compounds that affect the activity of D 24(28) sterol methyl reductase (SMR) and/or D (24) -sterol methyl transferase (SMT), and (e) specific primers for the molecular detection of P. brasiliensis in vitro and in clinical samples.

Melanin Protects Paracoccidioides brasiliensis from the Effects of Antimicrobial Photodynamic Inhibition and Antifungal Drugs

“…The treatment of PCM is usually long term (15), and there are few drugs available, the most common being a combination of sulfamethoxazole-trimethoprim, amphotericin B (AMB), and azoles (mainly itraconazole [ITC]). However, none of these is able to prevent clinical failure or relapse (1,15).…”

“…However, none of these is able to prevent clinical failure or relapse (1,15). In this context, the search for alternative treatment is important, and antimicrobial photodynamic inhibition (aPI) may be a promising option, particularly to treat skin lesions and oral mucosa.…”

The Paracoccidioides Cell Wall: Past and Present Layers Toward Understanding Interaction with the Host

“…Paracoccidioides has a single β-1,3-glucan synthase gene that is overexpressed in Pb01 yeasts (Tomazett et al, 2010); however, echinocandin inhibitors of β-1,3-glucan synthesis have little effect against the yeast pathogenic phase due to the prevalence of α-glucan (San Blas and Niño-Vega, 2008; Rodríguez-Brito et al, 2010). Thus, a better target would be α-1,3-glucan synthase and its regulatory molecules including GTPase proteins Rho1, Rho2, Rac1, and Cdc42 (Sorais et al, 2010).…”

Cross-Reactivity of Paracoccidioides brasiliensis , Histoplasma capsulatum , and Cryptococcus Species in the Commercial Platelia Aspergillus Enzyme Immunoassay

“…Galactomannan is a cell wall component for both the yeast and the mycelial forms of P. brasiliensis. In addition, H. capsulatum and P. brasiliensis are phylogenetically closely related fungi (7). Similarly for C. neoformans, the presence of an epitope causing cross-reactivity may also occur for C. gattii.…”