Exploration of Aspergillus fumigatus Ras pathways for novel antifungal drug targets

Frontiers in Microbiology
Qusai Al Abdallah, Jarrod R Fortwendel

Abstract

Ras pathway signaling is a critical virulence determinant for pathogenic fungi. Localization of Ras to the plasma membrane (PM) is required for Ras network interactions supporting fungal growth and virulence. For example, loss of Aspergillus fumigatus RasA signaling at the PM via inhibition of palmitoylation leads to decreased growth, altered hyphal morphogenesis, decreased cell wall integrity and loss of virulence. In order to be properly localized and activated, Ras proteins must transit a series of post-translational modification (PTM) steps. These steps include farnesylation, proteolytic cleavage of terminal amino acids, carboxymethylation, and palmitoylation. Because Ras activation drives tumor development, Ras pathways have been extensively studied in mammalian cells as a potential target for anti-cancer therapy. Inhibitors of mammalian Ras interactions and PTM components have been, or are actively being, developed. This review will focus on the potential for building upon existing scaffolds to exploit fungal Ras proteins for therapy, synthesizing data from studies employing both mammalian and fungal systems.

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Citations

Mar 28, 2018·Canadian Journal of Microbiology·David A SzalewskiRaúl G Barletta
Apr 11, 2017·Frontiers in Plant Science·Yaxiao Li, Baoxiu Qi
Aug 17, 2020·The Journal of Biological Chemistry·Emmanuelle V LeBlancLeah E Cowen

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Methods Mentioned

BETA
GTPase
nucleotide exchange
GTPases
lipidation

Software Mentioned

DNAstar
Lasergene

Related Concepts

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Aspergillosis (ASM)

Aspergillosis is the name given to a wide variety of diseases caused by infection by fungi of the genus Aspergillus. Aspergillosis occurs in chronic or acute forms which are clinically very distinct. Most cases of acute aspergillosis occur in patients with severely compromised immune systems. Chronic colonization or infection can cause complications in people with underlying respiratory illnesses. Discover the latest research on aspergillosis here.

Antifungals

An antifungal, also known as an antimycotic medication, is a pharmaceutical fungicide or fungistatic used to treat and prevent mycosis such as athlete's foot, ringworm, candidiasis, cryptococcal meningitis, and others. Discover the latest research on antifungals here.

Aspergillosis

Aspergillosis is the name given to a wide variety of diseases caused by infection by fungi of the genus Aspergillus. Aspergillosis occurs in chronic or acute forms which are clinically very distinct. Most cases of acute aspergillosis occur in patients with severely compromised immune systems. Chronic colonization or infection can cause complications in people with underlying respiratory illnesses. Discover the latest research on aspergillosis here.

Antifungals (ASM)

An antifungal, also known as an antimycotic medication, is a pharmaceutical fungicide or fungistatic used to treat and prevent mycosis such as athlete's foot, ringworm, candidiasis, cryptococcal meningitis, and others. Discover the latest research on antifungals here.