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Microsporidia and Acanthamoeba: the role of emerging corneal pathogens.

ABSTRACT: Parasitic organisms are increasingly recognized as human corneal pathogens. A notable increase in both well-defined Acanthamoeba keratitis and a more dramatic increase in reported cases of Microsporidia keratitis have suggested significant outbreaks of parasitic keratitis around the world. Historical and contemporary baselines as well as a familiar associated clinical presentation reinforce the significant outbreak of Acanthamoeba keratitis in the United States. The remarkable rise in cases of Microsporidia keratitis, however, lacks these established baselines and, further, describes a disease that is inconsistent with previous definitions of disease. While a well-defined, abrupt increase strongly suggests temporally related risk factors, most likely environmental, involved in the Acanthamoeba outbreak, the rise in Microsporidia keratitis suggests that increased awareness and improved diagnostic acumen are a significant factor in case ascertainment. Regardless, recent evidence indicates that both parasitic diseases are likely underreported in various forms of infectious keratitis, which may have unrecognized but significant implications in the pathogenesis of both primary protozoal and polymicrobial keratitis. Further understanding of the incidence and interaction of these organisms with current therapeutic regimens and more commonly recognized pathogens should significantly improve diagnosis and alter clinical outcomes.

SUBMITTER: Tu EY

PROVIDER: S-EPMC3272212 | biostudies-other | 2012 Feb

REPOSITORIES: biostudies-other

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Project description:BackgroundThe encystation of Acanthamoeba leads to the development of resilient cysts from vegetative trophozoites. This process is essential for the survival of parasites under unfavorable conditions. Previous studies have reported that, during the encystation of A. castellanii, the expression levels of encystation-related factors are upregulated. However, the regulatory mechanisms for their expression during the encystation process remains unknown. Proteins in the sirtuin family, which consists of nicotinamide adenine dinucleotide-dependent deacetylases, are known to play an important role in various cellular functions. In the present study, we identified the Acanthamoeba silent-information regulator 2-like protein (AcSir2) and examined its role in the growth and encystation of Acanthamoeba.MethodsWe obtained the full-length sequence for AcSir2 using reverse-transcription polymerase chain reaction. In Acanthamoeba transfectants that constitutively overexpress AcSir2 protein, SIRT deacetylase activity was measured, and the intracellular localization of AcSir2 and the effects on the growth and encystation of trophozoites were examined. In addition, the sirtuin inhibitor salermide was used to determine whether these effects were caused by AcSir2 overexpression RESULTS: AcSir2 was classified as a class-IV sirtuin. AcSir2 exhibited functional SIRT deacetylase activity, localized mainly in the nucleus, and its transcription was upregulated during encystation. In trophozoites, AcSir2 overexpression led to greater cell growth, and this growth was inhibited by treatment with salermide, a sirtuin inhibitor. When AcSir2 was overexpressed in the cysts, the encystation rate was significantly higher; this was also reversed with salermide treatment. In AcSir2-overexpressing encysting cells, the transcription of cellulose synthase was highly upregulated compared with that of control cells, and this upregulation was abolished with salermide treatment. Transmission electron microscope-based ultrastructural analysis of salermide-treated encysting cells showed that the structure of the exocyst wall and intercyst space was impaired and that the endocyst wall had not formed.ConclusionsThese results indicate that AcSir2 is a SIRT deacetylase that plays an essential role as a regulator of a variety of cellular processes and that the regulation of AcSir2 expression is important for the growth and encystation of A. castellanii.

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Microsporidia and Acanthamoeba: the role of emerging corneal pathogens.

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