CAREER: Examining bacterial filamentation as a mechanism for cell-to-cell spreading in an animal host

This award is funded in whole or in part under the American Rescue Plan Act of 2021 (Public Law 117-2).

Bacterial pathogens pose a continuing threat to health and agriculture, and a deeper understanding of how bacteria spread in a live animal can inform future therapies. Small transparent nematodes offer an opportunity to directly visualize bacterial infection and dissemination in the context of a live animal, allowing for the discovery of novel mechanisms that may be too difficult to visualize in more complex animals like mammals.

This proposal uses wild-isolated, microscopic nematodes and their associated microbiota to uncover novel host-microbe interactions. It focuses on dissecting the mechanisms governing a new paradigm for intracellular bacterial spreading between host cells, which was directly observed in a bacteria-infected wild nematode. The results from this project will serve as a technical roadmap for determining whether this paradigm for cell-cell spreading and the genetic pathway that controls it are conserved among other bacteria, which could provide novel strategies for treating bacterial infections and controlling environmental bacteria.

Early-stage undergraduates will conduct discovery-based research for this proposal and then create research-based STEM curriculum to teach at local high schools. This will create a cycle of research awareness among these undergraduates to help eliminate persistent psychological barriers about the accessibility of STEM research, especially among first-generation college students and those from low income areas.

This project focuses on a new intracellular bacterial pathogen, Bordetella atropi, that was observed in vivo to use a novel mechanism for cell-to-cell spreading in its host nematode Oscheius tipulae. After intestinal cell invasion, B. atropi converts from a coccobacillus to a filamentous morphology in order to invade multiple neighboring epithelial cells.

Filamentation by B. atropi requires the glucolipid pathway, a conserved glucose-sensing pathway used by bacteria to detect a nutrient-rich environment. This proposal will investigate the hypothesis that B. atropi uses nutrient sensing to detect host cell invasion, inhibit septation, and trigger filamentation for spreading to neighboring intestinal cells.

The specific aims are to (1) dissect the role of the glucolipid pathway in controlling filamentation through gene expression analysis, metabolite analysis, and cell biology; (2) understand the infection process of B. atropi by determining the fate of the lateral host membranes and identify host factors that promote filamentation, and (3) create a lab-based workshop that uses wild nematode sampling to discover other bacteria that filament in rich conditions and new intracellular bacterial pathogens of nematodes. This final education aim will have early-stage undergraduates conduct the research and then teach their discoveries at local high schools, making STEM-based research more accessible to young students.

This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.