? Microsporidia are obligate intracellular opportunistic protozoan pathogens that infect a wide range of vertebrates and invertebrates Although microsporidia have been known to cause disease in animals for more than 150 years, it was in conjunction with the AIDS epidemic that microsporidia were discovered as one of the causes of severe diarrhea in some HIV infected individuals The two most common causes of microsporidiosis in humans are Enterocytozoon bieneusi and Encephalitozoon intestinalis Because there is no established method for long term in vitro culture of E bieneusi, E intestinalis is used for these proposed studies When E intestinalis spores are placed in culture with host cells, the spores adhere to the host cell surfaces Although this adherence occurs seemingly spontaneously and can be viewed by light microscopy, it has not been described Preliminary studies show that E intestinalis spore adherence is specific and can be inhibited by the addition of exogenous glycosaminoglycans or short oligo peptides that contain an RGD (arg-gly-asp) cell attachment motif, indicating that spore adherence may be mediated by two different mechanisms While the optimal conditions for spore germination are not known, it seems logical that spore adherence may be a critical step in the infection process Thus, the overall objective of this research proposal is to characterize the adherence of E intestinalis spores to mammalian host cells and to determine the importance of adherence in the process of infection.
The Specific Aims which address the overall objective include (1) determining the mechanism(s) of E intestinalis spore adherence, and (2) clarifying the association of E intestinalis spore adherence and infectivity The results of these proposed studies will aid in elucidation of the biological significance of spore adherence as it relates to infectivity Understanding the mechanism of adherence could lead to the development of novel therapeutic interventions and to the prevention of infection and/or reinfection. ? ? ?
| Southern, Timothy R; Jolly, Carrie E; Russell Hayman, J (2006) Augmentation of microsporidia adherence and host cell infection by divalent cations. FEMS Microbiol Lett 260:143-9 |
| Hayman, J Russell; Southern, Timothy R; Nash, Theodore E (2005) Role of sulfated glycans in adherence of the microsporidian Encephalitozoon intestinalis to host cells in vitro. Infect Immun 73:841-8 |
