Encephalitozoon cuniculi Genotype III Evinces a Resistance to Albendazole Treatment in both Immunodeficient and Immunocompetent Mice

Antimicrob Agents Chemother. 2020 Apr 21;64(5):e00058-20. doi: 10.1128/AAC.00058-20. Print 2020 Apr 21.

Abstract

Of four genotypes of Encephalitozoon cuniculi, E. cuniculi genotype II is considered to represent a parasite that occurs in many host species in a latent asymptomatic form, whereas E. cuniculi genotype III seems to be more aggressive, and infections caused by this strain can lead to the death of even immunocompetent hosts. Although albendazole has been considered suitable for treatment of Encephalitozoon species, its failure in control of E. cuniculi genotype III infection has been reported. This study determined the effect of a 100× recommended daily dose of albendazole on an Encephalitozoon cuniculi genotype III course of infection in immunocompetent and immunodeficient mice and compared the results with those from experiments performed with a lower dose of albendazole and E. cuniculi genotype II. The administration of the regular dose of abendazole during the acute phase of infection reduced the number of affected organs in all strains of mice and absolute counts of spores in screened organs. However, the effect on genotype III was minor. Surprisingly, no substantial effect was recorded after the use of a 100× dose of albendazole, with larger reductions seen only in the number of affected organs and absolute counts of spores in all strains of mice, implying variations in albendazole resistance between these Encephalitozoon cuniculi genotypes. These results imply that differences in the course of infection and the response to treatment depend not only on the immunological status of the host but also on the genotype causing the infection. Understanding how microsporidia survive in hosts despite targeted antimicrosporidial treatment could significantly contribute to research related to human health.

Keywords: Encephalitozoon cuniculi; albendazole; genotype III; microsporidiosis; tolerance; treatment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Albendazole / administration & dosage
  • Albendazole / pharmacology*
  • Animals
  • Antifungal Agents / administration & dosage
  • Antifungal Agents / pharmacology*
  • CD4 Antigens / genetics
  • CD8 Antigens / genetics
  • Cell Line
  • Chlorocebus aethiops
  • Colony Count, Microbial
  • Disease Models, Animal
  • Encephalitozoon cuniculi / drug effects*
  • Encephalitozoon cuniculi / genetics*
  • Encephalitozoon cuniculi / isolation & purification
  • Encephalitozoonosis / drug therapy*
  • Genotype
  • Immunocompromised Host / immunology
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, SCID
  • Microbial Sensitivity Tests
  • Vero Cells

Substances

  • Antifungal Agents
  • CD4 Antigens
  • CD8 Antigens
  • Albendazole