Encephalitozoon intestinalis infection increases host cell mutation frequencyReport as inadecuate




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Infectious Agents and Cancer

, 8:43

Clinical oncology

Abstract

BackgroundMicrosporidia 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.

FindingsAs oxidative stress can lead to DNA damage, we hypothesized that E. intestinalis- infection would increase host cell nuclear mutation rate. Embryo fibroblasts from Big Blue 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.

ConclusionsThese 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.

KeywordsEncephalitozoon intestinalis Microsporidia infection Microsporidiosis Big Blue™ mouse Mutation frequency Opportunistic infections and cancer AbbreviationsE. intestinalisEncephalitozoon intestinalis

AIDSAcquired immunodeficiency syndrome

HIVHuman immunodeficiency virus

PVParasitophorous vacuole

BB-MEFBig Blue™ embryonic fibroblast

DMEMDulbecco’s modified Eagle’s medium

FBSFetal bovine serum

UVUltraviolet

E. intestinalisUVUV-inactivated E. intestinalis spores

hHours

hpiHours post-infection

H. hepaticusHelicobacter hepaticus

C. trachomatisChlamydia trachomatis

DAPI4’, 6-Diamidino-2-Phenylindole, Dichloride.

Electronic supplementary materialThe online version of this article doi:10.1186-1750-9378-8-43 contains supplementary material, which is available to authorized users.

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Author: Cory Ann Leonard - Maria Schell - Robert Vincent Schoborg - James Russell Hayman

Source: https://link.springer.com/







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