Mechanisms of Antifungal Resistance of ABC Transporator Genes in Aspergillus uessalvadorensis (2025)
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Date
2025-04-08
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KR Journal of Agriculture and Biosciences (IKRJAB)
Abstract
The present study on Aspergillus uessalvadorensis focuses on the characterization of the molecular mechanisms that give it a high adaptive capacity in highly toxic nvironments. Through a comprehensive genomic workflow, which included sequencing using high-throughput platforms (Illumina), expression analysis using qPCR, and functional annotation in bioinformatics tools such as InterProScan, UniProtKB, tBLASTn, UniRef90, MetaCyc, EggNOG, and KEGG, it was possible to
establish a robust relationship between genomic sequencing and the organism's adaptive strategies. The core of this fungus's resistance lies in the expansion and specialization of genes associated with multidrug efflux systems. In particular, the superfamily of ABC transporters (ATP-Binding Cassette), highly specialized membrane proteins that function as active expulsion pumps, stands out. These are composed of transmembrane domains (TMDs), responsible for substrate recognition and transport, and cytoplasmic nucleotide-binding domains (NBDs), responsible for ATP hydrolysis that drives the conformational change necessary for transport. In addition, the presence of transporters belonging to the Major Facilitator Superfamily (MFS) was identified, which operate through electrochemical gradients. This coexistence suggests a strategy of functional redundancy and specialization: while ABC systems participate in the active expulsion of more complex compounds, MFS
transporters contribute to cellular homeostasis and the handling of simpler metabolites. A relevant finding is the identification of a large protein (~2450 amino acids) that contains conserved domains associated with transport and regulation. In addition, genes encoding components of the DNA repair system, such as ABC excinuclease
subunits, were detected. Although these are not directly involved in the efflux of toxic compounds, they play a crucial role in repairing damage induced by oxidative stress, UV radiation, or other environmental agents. This shows a comprehensive defense
system that combines exclusion (eflux) mechanisms with tolerance and genomic repair strategies. From an ecological perspective, factors such as exposure to soils with a high concentration of heavy metals and the intensive use of fungicides could have exerted
selective pressure, favoring the expansion of these transport systems. In this sense, the identified transporters would not only be involved in resistance to antifungal compounds, but also in the regulation of ionic homeostasis and adaptation to extreme environments. In mechanistic terms, the operation of ABC transporters can be
described as a cyclical process: after the entry of a potentially toxic compound into the cell, the substrate is recognized by the transmembrane domains. Subsequently, the NBD domains hydrolyze ATP (ATP → ADP + Pi), generating the energy necessary to
induce a conformational change in the protein, allowing the active expulsion of the compound to the outside of the cell. This mechanism is one of the main barriers to antimicrobial agents. In conclusion, the genomic profile of A. uessalvadorensis reveals
a complex and multifactorial molecular architecture oriented to survival in adverse environments. However, although genomic evidence suggests a high potential for resistance, it is imperative to validate these findings through experimental studies,
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Keywords
ABC Multridrog Transporter, Aspergillus uessalvadorensis, MFS Major Facilitator Superfamily, Illumina, InterProScan.