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Central Role of the Trehalose Biosynthesis Pathway in the Pathogenesis of Human Fungal Infections: Opportunities and Challenges for Therapeutic Development.

Publication ,  Journal Article
Thammahong, A; Puttikamonkul, S; Perfect, JR; Brennan, RG; Cramer, RA
Published in: Microbiol Mol Biol Rev
June 2017

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.

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Published In

Microbiol Mol Biol Rev

DOI

EISSN

1098-5557

Publication Date

June 2017

Volume

81

Issue

2

Location

United States

Related Subject Headings

  • Virulence Factors
  • Virulence
  • Trehalose
  • Phosphoric Monoester Hydrolases
  • Microbiology
  • Invasive Fungal Infections
  • Humans
  • Host-Pathogen Interactions
  • Glucosyltransferases
  • Fungi
 

Citation

APA
Chicago
ICMJE
MLA
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Thammahong, A., Puttikamonkul, S., Perfect, J. R., Brennan, R. G., & Cramer, R. A. (2017). Central Role of the Trehalose Biosynthesis Pathway in the Pathogenesis of Human Fungal Infections: Opportunities and Challenges for Therapeutic Development. Microbiol Mol Biol Rev, 81(2). https://doi.org/10.1128/MMBR.00053-16
Thammahong, Arsa, Srisombat Puttikamonkul, John R. Perfect, Richard G. Brennan, and Robert A. Cramer. “Central Role of the Trehalose Biosynthesis Pathway in the Pathogenesis of Human Fungal Infections: Opportunities and Challenges for Therapeutic Development.Microbiol Mol Biol Rev 81, no. 2 (June 2017). https://doi.org/10.1128/MMBR.00053-16.
Thammahong A, Puttikamonkul S, Perfect JR, Brennan RG, Cramer RA. Central Role of the Trehalose Biosynthesis Pathway in the Pathogenesis of Human Fungal Infections: Opportunities and Challenges for Therapeutic Development. Microbiol Mol Biol Rev. 2017 Jun;81(2).
Thammahong, Arsa, et al. “Central Role of the Trehalose Biosynthesis Pathway in the Pathogenesis of Human Fungal Infections: Opportunities and Challenges for Therapeutic Development.Microbiol Mol Biol Rev, vol. 81, no. 2, June 2017. Pubmed, doi:10.1128/MMBR.00053-16.
Thammahong A, Puttikamonkul S, Perfect JR, Brennan RG, Cramer RA. Central Role of the Trehalose Biosynthesis Pathway in the Pathogenesis of Human Fungal Infections: Opportunities and Challenges for Therapeutic Development. Microbiol Mol Biol Rev. 2017 Jun;81(2).

Published In

Microbiol Mol Biol Rev

DOI

EISSN

1098-5557

Publication Date

June 2017

Volume

81

Issue

2

Location

United States

Related Subject Headings

  • Virulence Factors
  • Virulence
  • Trehalose
  • Phosphoric Monoester Hydrolases
  • Microbiology
  • Invasive Fungal Infections
  • Humans
  • Host-Pathogen Interactions
  • Glucosyltransferases
  • Fungi