Emerging understanding of the rat flea response to Yersinia pestis infection

PROJECT SUMMARY Fleas are obligate blood-feeding arthropods that are associated with several notable bacterial-derived human diseases, i.e. rickettsioses, bartonelloses, and plague. Plague caused by the Gram negative bacterium, Yersinia pestis, is difficult to eradicate because flea-borne transmission is endemic in natural foci of wild rodents and their associated fleas world-wide. Insecticide control is the primary strategy for disease management, but like many vector-borne diseases this is compromised by development of insecticide resistance in fleas. Development of novel vector-based strategies for bacterial pathogen control are therefore a priority. However, to accomplish this, we must overcome the dearth in knowledge regarding flea biology, particularly the detailed processes of the flea host response to infection. Towards this goal our lab has recently made novel observations that the Y. pestis factor Ymt is involved in manipulating the bloodmeal digestion processes related to detoxification of heme in a blood source dependent manner. Our goals are to understand the Ymt-mediated flea responses to infection that underlie successful Y. pestis infection of rat fleas. Therefore, our central hypothesis is that Ymt modulates mouse blood digestion processes related to heme detoxification and antioxidant defense to enable Y. pestis infection in rat fleas. Two aims will test this hypothesis. In Aim 1 we will determine if bloodmeal derived heme is correlated with flea ROS-mediated immune responses in a Ymt and blood source dependent manner. In Aim 2 we will use comparative transcriptomics to identify flea transcripts that are modulated in a Ymt-specific manner. Our proposed exploratory studies have potential to uncover biological processes related to blood digestion and immune processes in flea vectors that can be targeted to reduce establishment of transmissible infections to humans. Therefore, the proposed research lies within a part of the NIH's mission to develop fundamental knowledge that will assist in reducing the burden of infectious diseases on human health.