Protein kinases as potential anticandidal drug targets

Front Biosci (Landmark Ed). 2020 Mar 1;25(8):1412-1432. doi: 10.2741/4862.

Abstract

Candidal infections are increasing at an alarming rate due to hospital acquired infections causing high mortality rates worldwide. Moreover, the emergence of drug resistant Candida strains is the major impediment against effective therapeutics. Thus, there is an imperious need to search for novel antifungal drug targets. Among various fungi, Candida albicans is one of the most prevalent human fungal pathogen. Protein kinases modify other signaling molecules through phosphorylation and transduce extracellular stimuli for adaptation ensuing C. albicans growth, persistence and pathogenesis. In C. albicans, there are various kinds of kinases such as MAP (Mitogen Activated Protein) kinase cascade involving Hog1 (High-osmolarity glycerol) and Cek1 (C. albicans ERK-like Kinase1) mediated pathways, cyclin dependent pathway, cAMP (cyclic adenosine monophosphate) -dependent protein kinase pathway and TOR signaling pathway. Herein we have reviewed the variety of functions served by protein kinases in C. albicans. Additionally, we have discussed the inhibitors for targeting these kinases. Together, we explore the potential of these kinases as effective drug target and discuss the progress made in the development of inhibitors against these targets.

Publication types

  • Review

MeSH terms

  • Antifungal Agents / therapeutic use*
  • Biofilms / drug effects
  • Biofilms / growth & development
  • Candida albicans / drug effects*
  • Candida albicans / metabolism
  • Candida albicans / physiology
  • Candidiasis / drug therapy*
  • Candidiasis / microbiology
  • Fungal Proteins / antagonists & inhibitors*
  • Fungal Proteins / metabolism
  • Humans
  • Molecular Targeted Therapy / methods
  • Phosphorylation / drug effects
  • Protein Kinases / metabolism*
  • Signal Transduction / drug effects*

Substances

  • Antifungal Agents
  • Fungal Proteins
  • Protein Kinases