Glycobiology of Human Fungal Pathogens: New Avenues for Drug Development

Cells. 2019 Oct 30;8(11):1348. doi: 10.3390/cells8111348.

Abstract

Invasive fungal infections (IFI) are an increasing threat to the developing world, with fungal spores being ubiquitous and inhaled every day. Some fungal species are commensal organisms that are part of the normal human microbiota, and, as such, do not pose a threat to the immune system. However, when the natural balance of this association is disturbed or the host's immune system is compromised, these fungal pathogens overtake the organism, and cause IFI. To understand the invasiveness of these pathogens and to address the growing problem of IFI, it is essential to identify the cellular processes of the invading organism and their virulence. In this review, we will discuss the prevalence and current options available to treat IFI, including recent reports of drug resistance. Nevertheless, the main focus of this review is to describe the glycobiology of human fungal pathogens and how various components of the fungal cell wall, particularly cell wall polysaccharides and glycoconjugates, are involved in fungal pathogenicity, their biosynthesis and how they can be potentially exploited to develop novel antifungal treatment options. We will specifically describe the nucleotide sugar transporters (NSTs) that are important in fungal survival and suggest that the inhibition of fungal NSTs may potentially be useful to prevent the establishment of fungal infections.

Keywords: GDP-Mannose; UDP-Galactofuranose; UDP-Xylose; UDP-glucuronic acid; aspergillus; candida; cryptococcus; immunosuppression; invasive fungal infection; nucleotide sugar transporter.

Publication types

  • Review

MeSH terms

  • Antifungal Agents / pharmacology*
  • Cell Wall / chemistry*
  • Drug Development*
  • Fungal Polysaccharides / metabolism*
  • Fungi / drug effects*
  • Fungi / metabolism
  • Glycomics*
  • Humans
  • Invasive Fungal Infections / drug therapy*
  • Invasive Fungal Infections / metabolism
  • Invasive Fungal Infections / microbiology

Substances

  • Antifungal Agents
  • Fungal Polysaccharides