title: Encephalitozoon intestinalis infection increases host cell mutation frequency.
abstract: BACKGROUND
  Microsporidia are obligate intracellular opportunistic fungi that cause significant pathology in immunocompromised hosts. However, 11 percent of immunocompetent individuals in the general population are microsporidia-seropositive, indicating that severe immune suppression may not be a prerequisite for infection. Encephalitozoon intestinalis is transmitted in contaminated water and initially infects gastro-intestinal enterocytes, leading to diarrheal disease. This organism can also disseminate to many other organs. A recent report suggests that microsporidia can establish persistent infections, which anti-fungal treatment does not eradicate. Like other intracellular pathogens, microsporidia infection stresses the host cell and infected individuals have elevated hydrogen peroxide and free radical levels.
  
  
  RESULTS
  As oxidative stress can lead to DNA damage, we hypothesized that E. intestinalis-infection would increase host cell nuclear mutation rate. Embryo fibroblasts from Big BlueTM transgenic mice were E. intestinalis-infected and host nuclear mutation frequency was determined by selection of temperature-sensitive c-II gene mutant λ phage. The host mutation frequency in E. intestinalis-infected cultures was 2.5-fold higher than that observed in either mock-infected cells or cells infected with UV-inactivated E. intestinalis spores.
  
  
  CONCLUSIONS
  These data provide the first evidence that microsporidia infection can directly increase host cellular mutation frequency. Additionally, some event in the microsporidia developmental cycle between host cell attachment and parasitophorous vacuole formation is required for the observed effect. As there is considerable evidence linking infection with other intracellular pathogens and cancer, future studies to dissect the mechanism by which E. intestinalis infection increases host mutation frequency are warranted.
authors.forename: Cory Ann
authors.initials: CA
authors.lastname: Leonard
authors.forename: Maria
authors.initials: M
authors.lastname: Schell
authors.forename: Robert Vincent
authors.initials: RV
authors.lastname: Schoborg
authors.affiliation: Department of Biomedical Sciences, James H, Quillen College of Medicine, East Tennessee State University, Johnson City, TN 37614-0579, USA. hayman@etsu.edu.
authors.forename: James Russell
authors.initials: JR
authors.lastname: Hayman