Aspartate semialdehyde dehydrogenase inhibition suppresses the growth of the pathogenic fungus <scp><i>Candida albicans</i></scp>

Dahal, Gopal P.; Launder, Dylan; McKeone, Katherine M. M.; Hunter, Joseph P.; Conti, Heather R.; Viola, Ronald E.

doi:10.1002/ddr.21682

Cited by 6 publications

(1 citation statement)

References 33 publications

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“…Because the aspartate pathway is absent in humans, ASADH can be a promising new target for antifungal research. Deleting the ASD gene encoding for ASADH significantly decreases the survival of C. albicans, establishing this enzyme as essential for this organism (Dahal and Viola, 2018;Dahal et al, 2020).…”

Section: Enzymesmentioning

confidence: 99%

Mechanistic Understanding of Candida albicans Biofilm Formation and Approaches for Its Inhibition

et al. 2021

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In recent years, the demand for novel antifungal therapies has increased several- folds due to its potential to treat severe biofilm-associated infections. Biofilms are made by the sessile microorganisms attached to the abiotic or biotic surfaces, enclosed in a matrix of exopolymeric substances. This results in new phenotypic characteristics and intrinsic resistance from both host immune response and antimicrobial drugs. Candida albicans biofilm is a complex association of hyphal cells that are associated with both abiotic and animal tissues. It is an invasive fungal infection and acts as an important virulent factor. The challenges linked with biofilm-associated diseases have urged scientists to uncover the factors responsible for the formation and maturation of biofilm. Several strategies have been developed that could be adopted to eradicate biofilm-associated infections. This article presents an overview of the role of C. albicans biofilm in its pathogenicity, challenges it poses and threats associated with its formation. Further, it discusses strategies that are currently available or under development targeting prostaglandins, quorum-sensing, changing surface properties of biomedical devices, natural scaffolds, and small molecule-based chemical approaches to combat the threat of C. albicans biofilm. This review also highlights the recent developments in finding ways to increase the penetration of drugs into the extracellular matrix of biofilm using different nanomaterials against C. albicans.

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Section: Enzymesmentioning

confidence: 99%

Mechanistic Understanding of Candida albicans Biofilm Formation and Approaches for Its Inhibition

et al. 2021

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Bridging drug discovery through hierarchical subtractive genomics against asd, trpG, and secY of pneumonia causing MDR Staphylococcus aureus

Wisal,

Saeed,

Aurongzeb

et al. 2024

Mol Genet Genomics

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Staphylococcus aureus (S. aureus) is an opportunistic gram-positive, non-motile, and non-sporulating bacteria that induce pneumonia, a provocative lung infection affecting mainly the terminal bronchioles and the small air sacs known as alveoli. Recently, S. aureus has developed resistance to the available antibiotics consortium as per WHO reports, thereby, novel remedial targets and strong medications to forestall and cure this illness are desperately needed.Here, using pangenomics, a total of 1,387 core proteins were identi ed. Subtractive proteome analysis is utilized to further identify 12 proteins that are vital for bacteria. One membrane protein (secY) and two cytoplasmic proteins (asd and trpG) were chosen as possible therapeutic targets with respect to minimum % host identity, essentiality, and other cutoff values such as high resistance in MDR S. aureus. The amino acid sequence of selected targets was modeled and then docked against drug-like chemical libraries. The top-ranked compounds i.e., ZINC82049692, ZINC85492658 and 3a of Isosteviol derivative for Aspartatesemialdehyde dehydrogenase (asd); ZINC38222743, ZINC70455378, and 5m Isosteviol derivative for Anthranilate synthase component II (trpG); and nally, ZINC72292296, ZINC85632684, and 7m Isosteviol derivative for Protein translocase subunit SecY (secY), were further subjected to molecular dynamics studies for thermodynamic stability and validation. In this study, we discovered new therapeutic targets in S. aureus, some of which have previously been reported in other pathogenic microorganisms. Owing to further experimental validation, We anticipate that our method and results will make major contributions in the discovery of novel drugs and their targets in S. aureus-caused pneumonia.

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Structural–functional analysis of drug target aspartate semialdehyde dehydrogenase

Kumar,

Diwakar

et al. 2024

Drug Discovery Today

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Aspartate semialdehyde dehydrogenase inhibition suppresses the growth of the pathogenic fungus Candida albicans

Cited by 6 publications

References 33 publications

Mechanistic Understanding of Candida albicans Biofilm Formation and Approaches for Its Inhibition

Mechanistic Understanding of Candida albicans Biofilm Formation and Approaches for Its Inhibition

Bridging drug discovery through hierarchical subtractive genomics against asd, trpG, and secY of pneumonia causing MDR Staphylococcus aureus

Structural–functional analysis of drug target aspartate semialdehyde dehydrogenase

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