Publication:
Central role of the trehalose biosynthesis pathway in the pathogenesis of human fungal infections: Opportunities and challenges for therapeutic development

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Issued Date

2017

Resource Type

Review

File Type

application/pdf

ISSN

10922172

DOI

10.1128/MMBR.00053-16

Other identifier(s)

2-s2.0-85019796176

Rights Holder(s)

มหาวิทยาลัยศรีนครินทรวิโรฒ

Bibliographic Citation

Microbiology and Molecular Biology Reviews. Vol 81, No.2 (2017)

Suggested Citation

Thammahong A., Puttikamonkul S., Perfect J.R., Brennan R.G., Cramer R.A. Central role of the trehalose biosynthesis pathway in the pathogenesis of human fungal infections: Opportunities and challenges for therapeutic development. Microbiology and Molecular Biology Reviews. Vol 81, No.2 (2017). doi:10.1128/MMBR.00053-16 Retrieved from: https://hdl.handle.net/20.500.14740/4159

Title

Central role of the trehalose biosynthesis pathway in the pathogenesis of human fungal infections: Opportunities and challenges for therapeutic development

Author(s)

Thammahong A.
 Puttikamonkul S.
 Perfect J.R.
 Brennan R.G.
 Cramer R.A.

Abstract

Invasive fungal infections cause significant morbidity and mortality in part due to a limited antifungal drug arsenal. One therapeutic challenge faced by clinicians is the significant host toxicity associated with antifungal drugs. Another challenge is the fungistatic mechanism of action of some drugs. Consequently, the identification of fungus-specific drug targets essential for fitness in vivo remains a significant goal of medical mycology research. The trehalose biosynthetic pathway is found in a wide variety of organisms, including human-pathogenic fungi, but not in humans. Genes encoding proteins involved in trehalose biosynthesis are mechanistically linked to the metabolism, cell wall homeostasis, stress responses, and virulence of Candida albicans, Cryptococcus neoformans, and Aspergillus fumigatus. While there are a number of pathways for trehalose production across the tree of life, the TPS/TPP (trehalose-6-phosphate synthase/trehalose-6-phosphate phosphatase) pathway is the canonical pathway found in human-pathogenic fungi. Importantly, data suggest that proteins involved in trehalose biosynthesis play other critical roles in fungal metabolism and in vivo fitness that remain to be fully elucidated. By further defining the biology and functions of trehalose and its biosynthetic pathway components in pathogenic fungi, an opportunity exists to leverage this pathway as a potent antifungal drug target. The goal of this review is to cover the known roles of this important molecule and its associated biosynthesis-encoding genes in the human-pathogenic fungi studied to date and to employ these data to critically assess the opportunities and challenges facing development of this pathway as a therapeutic target. © Copyright 2017 American Society for Microbiology. All Rights Reserved.

Subject(s)

Trehalase
 Trehalose
 Trehalose 6 phosphate phosphatase
 Trehalose 6 phosphate synthase
 Unclassified drug
 Antifungal agent
 Glucosyltransferase
 Phosphatase
 Trehalose
 Trehalose-6-phosphate synthase
 Trehalose-phosphatase
 Virulence factor
 Carbohydrate synthesis
 Fungus
 Glycobiology
 Human
 Molecular pathology
 Mycosis
 Nonhuman
 Regulatory mechanism
 Review
 Aspergillus fumigatus
 Biosynthesis
 Candida albicans
 Cryptococcus neoformans
 Drug development
 Drug effects
 Genetics
 Host pathogen interaction
 Invasive Fungal Infections
 Metabolism
 Microbiology
 Pathogenicity
 Virulence
 Antifungal Agents
 Aspergillus fumigatus
 Biosynthetic Pathways
 Candida albicans
 Cryptococcus neoformans
 Drug Discovery
 Fungi
 Glucosyltransferases
 Host-Pathogen Interactions
 Humans
 Invasive Fungal Infections
 Phosphoric Monoester Hydrolases
 Trehalose
 Virulence
 Virulence Factors

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URI

https://hdl.handle.net/20.500.14740/4159

Collections

Scopus: Year 1983-2021

Endorsement

Review

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