Comparison of in vivo pathogenicity of four Candida auris clades in a neutropenic bloodstream infection murine model

Emerg Microbes Infect. 2020 Dec;9(1):1160-1169. doi: 10.1080/22221751.2020.1771218.

Abstract

Candida auris is an emerging worldwide concern, but comparative data about the virulence of different C. auris lineages in mammalian hosts is lacking. Different isolates of the four prevalent C. auris clades (South Asian n = 5, East Asian n = 4, South African n = 5, and South American n = 5) were compared to assess their virulence in a neutropenic murine bloodstream infection model with C. albicans as reference. C. auris, regardless of clade, proved to be less virulent than C. albicans. Highest overall mortality at day 21 was observed for the South American clade (96%), followed by the South Asian (80%), South African (45%) and East Asian (44%) clades. Fungal burden results showed close correlation with lethality. Histopathological examination revealed large aggregates of blastoconidia and budding yeast cells in the hearts, kidneys and livers but not in the spleens. The myocardium of apparently healthy sacrificed mice as well as of mice found moribund showed contraction band necrosis in case of all lineages. Regardless of clade, the heart and kidneys were the most heavily affected organs. Isolates of the same clade showed differences in virulence in mice, but a markedly higher virulence of the South American clade was clearly demonstrated.

Keywords: Virulence; aggregating Candida auris; contraction band necrosis; fungal tissue burden; myocardial involvement.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Antifungal Agents
  • Bacterial Load
  • Candida / classification
  • Candida / pathogenicity*
  • Candida albicans / pathogenicity
  • Candidemia / microbiology*
  • Disease Models, Animal
  • Heart / microbiology
  • Kidney / microbiology
  • Kidney / pathology
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Necrosis / microbiology
  • Neutropenia / microbiology*
  • Virulence

Substances

  • Antifungal Agents

Grants and funding

Z. T. and F. N. were supported by the EFOP-3.6.3-VEKOP-16-2017-00009 Program. R. K. was supported by the TA'MOP 4.2.4.A/2-11-1-2012-0001 National Excellence Program (Elaborating and operating an inland student and researcher personal support system). The project was subsidized by the European Union and co-financed by the European Social Fund. Z. T. and F. N. were supported by the U'NKP-19–3 New National Excellence Program of the Ministry of Human Capacities.