Proteomics of Cryptococcus neoformans: From the Lab to the Clinic

Int J Mol Sci. 2021 Nov 17;22(22):12390. doi: 10.3390/ijms222212390.

Abstract

Fungal pathogens cause an array of diseases by targeting both immunocompromised and immunocompetent hosts. Fungi overcome our current arsenal of antifungals through the emergence and evolution of resistance. In particular, the human fungal pathogen, Cryptococcus neoformans is found ubiquitously within the environment and causes severe disease in immunocompromised individuals around the globe with limited treatment options available. To uncover fundamental knowledge about this fungal pathogen, as well as investigate new detection and treatment strategies, mass spectrometry-based proteomics provides a plethora of tools and applications, as well as bioinformatics platforms. In this review, we highlight proteomics approaches within the laboratory to investigate changes in the cellular proteome, secretome, and extracellular vesicles. We also explore regulation by post-translational modifications and the impact of protein-protein interactions. Further, we present the development and comprehensive assessment of murine models of cryptococcal infection, which provide valuable tools to define the dynamic relationship between the host and pathogen during disease. Finally, we explore recent quantitative proteomics studies that begin to extrapolate the findings from the bench to the clinic for improved methods of fungal detection and monitoring. Such studies support a framework for personalized medical approaches to eradicate diseases caused by C. neoformans.

Keywords: Cryptococcus neoformans; fungal pathogenesis; in vitro and in vivo models; mass spectrometry-based proteomics; personalized medicine.

Publication types

  • Review

MeSH terms

  • Animals
  • Antifungal Agents / therapeutic use
  • Cryptococcosis / drug therapy
  • Cryptococcosis / metabolism*
  • Cryptococcosis / microbiology
  • Cryptococcus neoformans / genetics
  • Cryptococcus neoformans / metabolism*
  • Cryptococcus neoformans / pathogenicity
  • Disease Models, Animal
  • Drug Resistance, Fungal / genetics
  • Extracellular Vesicles / metabolism
  • Fungal Proteins / genetics
  • Fungal Proteins / metabolism*
  • Host-Parasite Interactions / genetics
  • Humans
  • Mice
  • Precision Medicine / methods
  • Protein Interaction Maps / genetics
  • Protein Processing, Post-Translational / genetics
  • Proteome / genetics
  • Proteome / metabolism*
  • Proteomics / methods*
  • Secretome / metabolism
  • Transcriptome
  • Treatment Outcome
  • Virulence Factors / metabolism

Substances

  • Antifungal Agents
  • Fungal Proteins
  • Proteome
  • Virulence Factors