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Keir M Balla

Publications and source records attributed to Keir M Balla.

2 recordsLinked to original sources

Identification of microsporidia host-exposed proteins reveals a repertoire of large paralogous gene families and rapidly evolving proteins

Pathogens use a variety of secreted and surface proteins to interact with and manipulate their hosts, but a systematic approach for identifying such proteins has been lacking. To identify these host-exposed proteins, we used spatially restricted enzymatic tagging followed by mass spectrometry analysis of C. elegans infected with two species of Nematocida microsporidia. We identified 82 microsporidia proteins inside of intestinal cells, including several pathogen proteins in the nucleus. These microsporidia proteins are enriched in targeting signals, are rapidly evolving, and belong to large, Nematocida-specific gene families. We also find that large, species-specific families are common throughout microsporidia species. Our data suggest that the use of a large number of rapidly evolving species-specific proteins represents a common strategy for these intracellular pathogens to interact with their hosts. The unbiased method described here for identifying potential pathogen effectors represents a powerful approach for the study of a broad range of pathogens.

Evolutionary Biology

Cell-to-cell spread of microsporidia causes C. elegans organs to form syncytia

The growth of pathogens is dictated by their interactions with the host environment. Many obligate intracellular pathogens undergo several cellular decisions as they progress through their life cycles inside of host cells. We studied this process for several species of microsporidia in the genus Nematocida in their co-evolved animal host Caenorhabditis elegans. We found that microsporidia can restructure multicellular host tissues into a single contiguous multinucleate cell. In particular, we found that all three Nematocida species we studied were able to spread across the cells of C. elegans tissues before forming spores, with two species causing syncytial formation in the intestine, and one species causing syncytial formation in the muscle. We also found that the decision to switch from replication to differentiation in N. parisii was altered by the density of infection, suggesting that environmental cues influence the dynamics of the pathogen life cycle. These findings show how microsporidia can maximize the use of host space for growth, and that environmental cues in the host can regulate a developmental switch in the pathogen.

Cell Biology