Amino Acid Metabolism and Transport Mechanisms as Potential Antifungal Targets

McCarthy, Matthew W; Walsh, Thomas J.

doi:10.3390/ijms19030909

Cited by 38 publications

(27 citation statements)

References 86 publications

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“…Another option would be targeting or exploiting fungal amino acid transport mechanisms. A current review of this strategy can be found here [109].…”

Section: Amino Acid Metabolism As a Potential Drug Targetmentioning

confidence: 99%

Role of Amino Acid Metabolism in the Virulence of Human Pathogenic Fungi

Garbe

Vylkova

2019

Curr Clin Micro Rpt

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Purpose of the Review The success of Candida albicans, Aspergillus fumigatus, and Cryptococcus neoformans as fungal pathogens depends on their rapid adaptation to host microenvironments, through metabolic remodeling, stress resistance, and expression of virulence determinants. Amino acids represent an abundant nitrogen and carbon source within the host; however, their acquisition by fungi is a very complex process that interconnects several sensory and uptake systems and downstream pathways. In this review, we will summarize the current knowledge concerning this topic, identify gaps or discrepancies, and discuss future research directions. Recent Findings Aside from supporting basic cellular functions, the utilization of many amino acids has a direct effect on fungal pathogenicity by triggering key virulence traits, including hyphal morphogenesis and biofilm growth in C. albicans, capsule formation in C. neoformans, and melanization in A. fumigatus. Summary Although many components of amino acid sensing and metabolism are fungal specific, their importance in infection and potential as candidates for antifungal drug development require further investigation.

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“…Another option would be targeting or exploiting fungal amino acid transport mechanisms. A current review of this strategy can be found here [109].…”

Section: Amino Acid Metabolism As a Potential Drug Targetmentioning

confidence: 99%

Role of Amino Acid Metabolism in the Virulence of Human Pathogenic Fungi

Garbe

Vylkova

2019

Curr Clin Micro Rpt

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“…More focused studies are needed to find which mechanism is involved in differential metabolites having amino acids, lipids, fatty acids, tricarboxylic acid (TCA) cycle, purines, starch and sucrose were observed in both PiCB-treated and control mycelia (Table S1 and Figure 4). Amino acids are the important nutritional source for the P. digitatum, and their metabolic pathways may be targeted to check the fungal growth [33,34]. Among the 23 amino acids detected in P. digitatum mycelia, 18 amino acids were increased, while five amino acids were significantly decreased in PiCB-treated samples compared with the respective controls (Table S1 and Figure 4).…”

Section: Effects Of Picb On the Metabolic Profiles Of P Digitatum Mymentioning

confidence: 99%

UHPLC-Q-TOF/MS-Based Metabolomics Approach Reveals the Antifungal Potential of Pinocembroside against Citrus Green Mold Phytopathogen

Chen

Cai

Chen

et al. 2019

Plants

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Pinocembroside (PiCB) isolated from Ficus hirta Vahl. fruit was studied herein with the aim to find the potential mechanism for significant inhibition of growth of Penicillium digitatum, a causative pathogen of citrus green mold disease. PiCB substantially inhibited mycelial growth of P. digitatum, with the observed half maximal effective concentration (EC 50 ), minimum inhibitory concentration (MIC), and minimum fungicidal concentration (MFC) of 120.3, 200, and 400 mg/L, respectively. Moreover, PiCB altered hyphal morphology and cellular morphology by breaking and shrinking of mycelia, decomposing cell walls, cytoplasmic inclusions. In addition to, a non-targeted metabolomics analysis by UHPLC-Q-TOF/MS was also performed, which revealed that PiCB treatment notably disrupted the metabolisms of amino acids, lipids, fatty acids, TCA, and ribonucleic acids, thereby contributing to membrane peroxidation. Current findings provide a new perception into the antifungal mechanism of PiCB treatment in inhibiting P. digitatum growth through membrane peroxidation.

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“…Among these ligands, Sadenosyl-L-methionine is used for a therapeutic against depression, liver disorders, fibromyalgia, and osteoarthritis [64], but also is an authentic substrate for this enzyme. Sinefungin is a natural drug produced by Streptomyces griseolus and experimentally used as antibiotics [65][66][67] (Fig. 3A).…”

Section: '-O-ribose Methyltransferasementioning

confidence: 99%

Knowledge‐based structural models of SARS‐CoV‐2 proteins and their complexes with potential drugs

et al. 2020

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Edited by John BriggsThe World Health Organization (WHO) has declared the coronavirus disease 2019 (COVID-19) caused by the novel coronavirus SARS-CoV-2 a pandemic. There is, however, no confirmed anti-COVID-19 therapeutic currently. In order to assist structure-based discovery efforts for repurposing drugs against this disease, we constructed knowledge-based models of SARS-CoV-2 proteins and compared the ligand molecules in the template structures with approved/experimental drugs and components of natural medicines. Our theoretical models suggest several drugs, such as carfilzomib, sinefungin, tecadenoson, and trabodenoson, that could be further investigated for their potential for treating COVID-19.

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Amino Acid Metabolism and Transport Mechanisms as Potential Antifungal Targets

Cited by 38 publications

References 86 publications

Role of Amino Acid Metabolism in the Virulence of Human Pathogenic Fungi

Role of Amino Acid Metabolism in the Virulence of Human Pathogenic Fungi

UHPLC-Q-TOF/MS-Based Metabolomics Approach Reveals the Antifungal Potential of Pinocembroside against Citrus Green Mold Phytopathogen

Knowledge‐based structural models of SARS‐CoV‐2 proteins and their complexes with potential drugs

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