Unlocking the therapeutic potential of the fungal cell wall: Clinical implications and drug resistance

Chibuike Ibe, Louise A. Walker, Neil A.R. Gow, Carol A. Munro*

*Corresponding author for this work

Research output: Chapter in Book/Report/Conference proceedingChapter

3 Citations (Scopus)

Abstract

The cell wall of Candida albicans is essential for cellular survival. The wall is a rich polysaccharide and mannoprotein complex. During wall synthesis, the cell wall components-glucan, chitin and mannoproteins-are assembled and stabilised in the cell wall space by the action of cell wall-associated enzymes and structural wall proteins. Cell surface proteins are also important in C. albicans virulence. The components of the cell wall are unique to fungi, thus making the wall an attractive drug target. Echinocandins are antifungal drugs that inhibit the synthesis of cell wall b-1,3-D-glucan and are fungicidal to C. albicans. Echinocandin treatment, at sub-inhibitory concentrations, can result in a compensatory increase in wall chitin content and triggers the expression of mannoproteins whose activities remodel the wall. C. albicans cells with thicker cell walls and elevated chitin levels are less susceptible to echinocandin therapy. The development of a molecule that non-competitively inhibits chitin synthesis and/or impairs cell wall integrity response regulatory pathways may impact the cell wall in such a way that reduces its compensatory ability. This type of molecule may have a synergistic effect in combined therapy with other cell wall inhibitors such as b-1,3-D-glucan-targeting antifungal drugs for managing candidiasis infections. The synthesis and localisation of mannoproteins at the cell surface also provide an attractive cell wall target for future antifungal agents.

Original languageEnglish
Title of host publicationCandida albicans
Subtitle of host publicationCellular and Molecular Biology: Second Edition
EditorsR Prasad
PublisherSpringer International Publishing AG
Pages313-346
Number of pages34
ISBN (Electronic)9783319504094
ISBN (Print)9783319504087
DOIs
Publication statusPublished - 2017

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)

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    Ibe, C., Walker, L. A., Gow, N. A. R., & Munro, C. A. (2017). Unlocking the therapeutic potential of the fungal cell wall: Clinical implications and drug resistance. In R. Prasad (Ed.), Candida albicans: Cellular and Molecular Biology: Second Edition (pp. 313-346). Springer International Publishing AG. https://doi.org/10.1007/978-3-319-50409-4_16