Updates in Paracoccidioides Biology and Genetic Advances in Fungus Manipulation

Abstract

The dimorphic fungi of the Paracoccidioides genus are the causative agents of paracoccidioidomycosis (PCM). This disease is endemic in Latin America and primarily affects workers in rural areas. PCM is considered a neglected disease, despite being a disabling disease that has a notable impact on the public health system. Paracoccidioides spp. are thermally dimorphic fungi that present infective mycelia at 25 °C and differentiate into pathogenic yeast forms at 37 °C. This transition involves a series of morphological, structural, and metabolic changes which are essential for their survival inside hosts. As a pathogen, the fungus is subjected to several varieties of stress conditions, including the host immune response, which involves the production of reactive nitrogen and oxygen species, thermal stress due to temperature changes during the transition, pH alterations within phagolysosomes, and hypoxia inside granulomas. Over the years, studies focusing on understanding the establishment and development of PCM have been conducted with several limitations due to the low effectiveness of strategies for the genetic manipulation of Paracoccidioides spp. This review describes the most relevant biological features of Paracoccidioides spp., including aspects of the phylogeny, ecology, stress response, infection, and evasion mechanisms of the fungus. We also discuss the genetic aspects and difficulties of fungal manipulation, and, finally, describe the advances in molecular biology that may be employed in molecular research on this fungus in the future.