The putative autophagy regulator Atg7 affects the physiology and pathogenic mechanisms of Cryptococcus neoformans

Future Microbiol. 2016 Oct:11:1405-1419. doi: 10.2217/fmb-2016-0090. Epub 2016 Oct 18.

Abstract

Aim: We investigated the involvement of the autophagy protein 7 (Atg7) in physiology and pathogenic potential of Cryptococcus neoformans.

Materials & methods: The C. neoformans gene encoding Atg7 was deleted by biolistic transformation for characterization of autophagy mechanisms, pigment formation, cell dimensions, interaction with phagocytes and pathogenic potential in vivo.

Results & conclusion: ATG7 deletion resulted in defective autophagy mechanisms, enhanced pigmentation and increased cellular size both in vitro and in vivo. The atg7Δ mutant had decreased survival in the lung of infected mice, higher susceptibility to the killing machinery of different host phagocytes and reduced ability to kill an invertebrate host. These results connect Atg7 with mechanisms of pathogenicity in the C. neoformans model.

Keywords: ATG7; Cryptococcus neoformans; autophagy; macrophages; virulence.

MeSH terms

  • Animals
  • Arthropods / microbiology
  • Autophagy / physiology*
  • Autophagy-Related Protein 7 / genetics
  • Autophagy-Related Protein 7 / physiology*
  • Cryptococcosis / microbiology*
  • Cryptococcosis / pathology
  • Cryptococcus neoformans / cytology
  • Cryptococcus neoformans / genetics
  • Cryptococcus neoformans / pathogenicity*
  • Cryptococcus neoformans / physiology*
  • DNA, Fungal
  • Disease Models, Animal
  • Female
  • Fungal Proteins / genetics
  • Gene Deletion
  • Gene Expression Regulation, Fungal
  • Genes, Fungal / genetics
  • Larva / microbiology
  • Lung / microbiology
  • Lung / pathology
  • Mice
  • Mice, Inbred C57BL
  • Nitrogen
  • Oxygen
  • Phagocytes
  • Pigments, Biological / biosynthesis
  • Sequence Deletion
  • Survival
  • Virulence

Substances

  • Atg7 protein, mouse
  • DNA, Fungal
  • Fungal Proteins
  • Pigments, Biological
  • Autophagy-Related Protein 7
  • Nitrogen
  • Oxygen