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.
Highlights
The evolution of microorganisms represents a continuous origin of emerging human pathogens, new strains of bacteria and fungi that become resistant to our current antibiotic and antifungal compounds.Among fungi, the order Mucorales is a source of antifungal resistance species identified as the causal agents for the lethal and emerging disease known as mucormycosis [1]
These results suggested a functional specialization of the high-affinity iron uptake mechanism in dimorphism, linking two crucial virulence determinants of mucormycosis
F1 and CYP51 F5), like it was reported in Aspergillus fumigatus [75]; and point mutations in these proteins might play a key role in the reduction of the affinity to one or more types of triazole drugs
Summary
The evolution of microorganisms represents a continuous origin of emerging human pathogens, new strains of bacteria and fungi that become resistant to our current antibiotic and antifungal compounds. The order Mucorales is a source of antifungal resistance species identified as the causal agents for the lethal and emerging disease known as mucormycosis [1]. Significant increases in mucormycosis cases, mortality rates of 90% in disseminated infections, and the lack of effective antifungal treatments have raised the alarm on this emerging disease. DNA can be introduced in Mucor circinelloides, Rhizopus delemar, and Rhizopus oryzae [6,7] These genetic models and the alarm raised for the emerging cases of mucormycosis are attracting the interest of the scientific community. We summarize the results of these studies, showing the main advances in the knowledge of Mucorales fungi, the disease that they produce, and the perspectives for the development of effective future treatments
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