Microsporidia Spore Adherence to Integrin Ligands

East Tennessee State University, Johnson City TN

Investigators

Abstract

Abstract: Microsporidia are obligate intracellular opportunistic fungal protists that are known pathogens of many animals, including humans. During the AIDS epidemic, microsporidia were found to be important pathogens of immune-suppressed individuals. Today, reports also show that immune-competent individuals can become infected. Host cell infection occurs when microsporidia activate and release a coiled hollow tube through which the infectious sporoplasm passes into the host cell cytoplasm. The mechanism of spore activation is unknown. However, in previous studies, we have shown that microsporidia adhere to the host cell surface. This adherence is mediated by host cell glycosaminoglycans (GAG) and a spore surface ligand called EnP1. Most importantly, when spores are prevented from adhering, infection of host cells decreases. These data shape our overall hypothesis that spores adherence is necessary for host cell infection. Upon further analysis it is apparent that a second mechanism of spore adherence, which involves host cell integrins, may exist. Preliminary data show that, in addition to exogenous GAGs, spore adherence can be inhibited by addition of either ?RGD- containing peptides, integrin blocking antibodies, or recombinant integrin protein. The use of co-receptors for pathogen recognition is not unique, as viruses often use more than one host receptor. In light of these data, the overall goals of this project are to examine and characterize host cell integrins as a possible receptor in microsporidia spore adherence and to identify candidate integrin ligands on the surface of spores. The results of this study will lead to a better understanding of the mechanisms of spore adherence as it may relate to activation and host cell infection, which will be useful in developing novel therapeutics.