Virulence factors of Paracoccidioides brasiliensis as therapeutic targets: a review

Antonie Van Leeuwenhoek. 2020 May;113(5):593-604. doi: 10.1007/s10482-019-01382-5. Epub 2020 Jan 4.

Abstract

Paracoccidiodomycosis (PCM) is a systemic mycosis caused by the fungus Paracoccidioides brasiliensis and Paracoccidioides lutzii. The disease requires long and complicated treatment. The aim of this review is to address the fungal virulence factors that could be the target of the development of new drugs for PCM treatment. Virulence factors favoring the process of fungal infection and pathogenicity are considered as a microbial attribute associated with host susceptibility. P. brasiliensis has some known virulence factors which are 43 kDa glycoprotein (gp 43) which is an important fungal antigen, 70 kDa glycoprotein (gp 70), the carbohydrates constituting the fungal cell wall α-1,3, glucan and β-1,3-glucan, cell adhesion molecules and the presence of melanin pigments. The discovery and development of drugs that interact with these factors, such as inhibitors of β-1,3-glucan, reduced synthesis of gp 43, inhibitors of melanin production, is of great importance for the treatment of PCM. The study of virulence factors favors the understanding of pathogen-host relationships, aiming to evaluate the possibility of developing new therapeutic targets and mechanisms that these molecules play in the infectious process, favoring the design of a more specific treatment for this disease.

Keywords: Paracoccidioides brasiliensis; Therapeutics targets; Virulence factors.

Publication types

  • Review

MeSH terms

  • Animals
  • Antifungal Agents / therapeutic use
  • Cell Wall / metabolism
  • Central America / epidemiology
  • Fungal Proteins / metabolism
  • Glucans / metabolism
  • Glycoproteins / metabolism
  • Host-Pathogen Interactions
  • Humans
  • Melanins / metabolism
  • Paracoccidioides* / drug effects
  • Paracoccidioides* / isolation & purification
  • Paracoccidioides* / metabolism
  • Paracoccidioides* / pathogenicity
  • Paracoccidioidomycosis* / epidemiology
  • Paracoccidioidomycosis* / metabolism
  • Paracoccidioidomycosis* / pathology
  • Paracoccidioidomycosis* / therapy
  • Prevalence
  • South America / epidemiology
  • Virulence Factors / metabolism*

Substances

  • Antifungal Agents
  • Fungal Proteins
  • Glucans
  • Glycoproteins
  • Melanins
  • Virulence Factors