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Published on: June 23, 2022
Fungal-Metal Interactions: A Review of Toxicity and Homeostasis
Janelle R Robinson1, Omoanghe S Isikhuemhen1, Felicia N Anike1
1Department of Natural Resources and Environmental Design, North Carolina Agricultural and Technical State University, 1601 East Market Street, Greensboro, NC 27411, USA.
Abstract:
Metal nanoparticles used as antifungals have increased the occurrence of fungal-metal interactions. However, there is a lack of knowledge about how these interactions cause genomic and physiological changes, which can produce fungal superbugs. Despite interest in these interactions, there is limited understanding of resistance mechanisms in most fungi studied until now. We highlight the current knowledge of fungal homeostasis of zinc, copper, iron, manganese, and silver to comprehensively examine associated mechanisms of resistance. Such mechanisms have been widely studied in Saccharomyces cerevisiae, but limited reports exist in filamentous fungi, though they are frequently the subject of nanoparticle biosynthesis and targets of antifungal metals. In most cases, microarray analyses uncovered resistance mechanisms as a response to metal exposure. In yeast, metal resistance is mainly due to the down-regulation of metal ion importers, utilization of metallothionein and metallothionein-like structures, and ion sequestration to the vacuole. In contrast, metal resistance in filamentous fungi heavily relies upon cellular ion export. However, there are instances of resistance that utilized vacuole sequestration, ion metallothionein, and chelator binding, deleting a metal ion importer, and ion storage in hyphal cell walls. In general, resistance to zinc, copper, iron, and manganese is extensively reported in yeast and partially known in filamentous fungi; and silver resistance lacks comprehensive understanding in both.
Insights
Fungal resistance to metals like zinc, copper, iron, and manganese is understood in yeast but less so in filamentous fungi. Silver resistance mechanisms remain largely unknown in both, impacting antifungal development.
Area of Science:
- Environmental Microbiology
- Mycology
- Biochemistry
Background:
- Metal nanoparticles are increasingly used as antifungals, leading to more fungal-metal interactions.
- Understanding these interactions is crucial for addressing the rise of fungal superbugs.
- Current knowledge of fungal resistance mechanisms to metals is limited, especially in filamentous fungi.
Purpose of the Study:
- To review and synthesize current knowledge on fungal homeostasis of essential metals (zinc, copper, iron, manganese) and silver.
- To comprehensively examine metal resistance mechanisms in yeast and filamentous fungi.
- To identify knowledge gaps, particularly concerning silver resistance and mechanisms in filamentous fungi.
Main Methods:
- Literature review and synthesis of existing research on fungal metal resistance.
- Analysis of microarray data to identify resistance mechanisms in response to metal exposure.
- Comparative examination of resistance strategies between Saccharomyces cerevisiae (yeast) and filamentous fungi.
Main Results:
- Metal resistance in yeast primarily involves down-regulation of importers, metallothionein use, and vacuolar sequestration.
- Filamentous fungi predominantly utilize cellular ion export for metal resistance, with some employing vacuolar sequestration and cell wall storage.
- Resistance to zinc, copper, iron, and manganese is well-documented in yeast but only partially understood in filamentous fungi; silver resistance is poorly understood in both.
Conclusions:
- Fungal resistance mechanisms vary significantly between yeast and filamentous fungi, with implications for antifungal development.
- Further research is needed to elucidate silver resistance pathways and expand understanding in filamentous fungi.
- Addressing knowledge gaps is critical for managing fungal infections and mitigating the emergence of antifungal resistance.
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