Genes, Pathways, and Mechanisms Involved in the Virulence of Mucorales

Abstract

The order Mucorales is a group of ancient fungi with limited tools for gene manipulation. The main consequence of this manipulation unwillingness is the limited knowledge about its biology compared to other fungal groups. However, the emerging of mucormycosis, a fungal infection caused by Mucorales, is attracting the medical spotlight in recent years because the treatments available are not efficient in reducing the high mortality associated with this disease. The result of this renewed interest in Mucorales and mucormycosis is an extraordinarily productive effort to unveil their secrets during the last decade. In this review, we describe the most compelling advances related to the genetic study of virulence factors, pathways, and molecular mechanisms developed in these years. The use of a few genetic study models has allowed the characterization of virulence factors in Mucorales that were previously described in other pathogens, such as the uptake iron systems, the mechanisms of dimorphism, and azole resistances. More importantly, recent studies are identifying new genes and mechanisms controlling the pathogenic potential of Mucorales and their interactions with the host, offering new alternatives to develop specific strategies against mucormycosis.

Keywords: CotH; Mucor; Mucorales; PKA; RNAi; Rhizopus; antifungal resistance; azole; azole resistance; calcineurin; dimorphism; epimutant; host-pathogen interactions; iron; lanolase; mucormycosis.

Figure 1

The interplay of calcineurin, protein kinase A (PKA), and iron uptake systems in dimorphism and virulence of Mucor circinelloides.

Figure 2

Diversity of RNA interfering (RNAi)-based pathways in Mucor circinelloides. RdRPs: RNA-dependent RNA polymerases; Dcl: Dicer enzymes; Ago: argonaute proteins; RnhA: Sad-3-like helicase; R3B2: RNaseIII domain (r3) and two dsRNA binding domain (b2); siRNAs: small interfering RNAs; esRNAs: endogenous small RNAs; rdRNAs rdrp-dependent dicer-independent RNAs.