|Our research focuses on understanding host-microbe interactions, specifically as related to plague pathogenesis. Yersinia pestis, the causative agent of plague, is a naturally occuring infection of some rodent populations. It is typically spread from rodent to rodent by their fleas. Humans may become an accidental host if they come into close contact with these infected animals or their fleas. Y. pestis has evolved to survive within each of these hosts (mammals and fleas) using a variety of virulence factors, all of which must be coordinated in response the host environment. Our work investigates factors that are important for Y. pestis survival in the mammalian host and the flea vector.|
Check out our latest pub:
Merritt,P.M. , T. Nero, L. Bohman, S. Felek, E. S. Krukonis, and M. M. Marketon. 2014. Yersinia pestis targets neutrophils via complement receptor 3. Cell. Microbiol. doi: 10.1111/cmi.12391. [Epub ahead of print]
Yersinia species display a tropism for lymphoid tissues during infection, and the bacteria select innate immune cells for delivery of cytotoxic effectors by the type III secretion system. Yet the mechanism for target cell selection remains a mystery. Here we investigate the interaction of Yersinia pestis with murine splenocytes to identify factors that participate in the targeting process. We find that interactions with primary immune cells rely on multiple factors. First, the bacterial adhesin Ail is required for efficient targeting of neutrophils in vivo. However, Ail does not appear to directly mediate binding to a specific cell type. Instead, we find that host serum factors direct Y. pestis to specific innate immune cells, particularly neutrophils. Importantly, specificity towards neutrophils was increased in the absence of bacterial adhesins due to reduced targeting of other cell types, but this phenotype was only visible in the presence of mouse serum. Addition of antibodies against complement receptor 3 and CD14 blocked target cell selection, suggesting that a combination of host factors participate in steering bacteria toward neutrophils during plague infection.