We are pleased to announce that Daria Van Tyne, PhD, has been awarded funding in the amount of $2,932,227 for a five-year grant by the National Institutes of Health/National Institute of Allergy and Infectious Diseases (NIH/NIAID) entitled “Adaptation of vancomycin-resistant enterococci during bloodstream infection.” This proposal was submitted in response to the funding opportunity entitled “NIH Research Project Grant (Parent R01 Clinical Trial Not Allowed)” under funding opportunity announcement PA-20-185.
Vancomycin-resistant Enterococcus faecium (VRE) is a frequent cause of bloodstream infection (BSI), particularly among immunocompromised and hospitalized patients. VRE-BSI 30-day mortality rates are greater than 30%, and they have not changed over the last 25 years. Concerningly, VRE infections are difficult to treat, and nearly one third of patients experience prolonged BSI (≥5 days) or recurrent infection within one year.
We propose to study the population-level evolutionary dynamics of VRE-BSI sampled from the GI tract and blood of infected patients, and to functionally characterize bacterial adaptations that promote VRE-BSI. Our central hypothesis is that VRE isolated from BSI possess genetic adaptations that enhance their survival in the blood. This proposal will establish an entirely new approach for infectious disease research; by studying VRE populations rather than individual clones, we will provide greater insight into bacterial evolutionary dynamics during infection. We will compare VRE populations sampled from the GI tract and the blood of the same patient, and will study how these populations differ from one another and change over time. Then we will identify candidate adaptive mutations that are associated with VRE-BSI, and will probe the molecular mechanisms underlying these mutations. Understanding this adaptation can reveal new targets for interventions to combat VRE-BSI.
Overall, this study has the potential to transform our understanding of how antibiotic-resistant bacteria adapt during human infection. In addition, the identification of bacterial genes and pathways under selection during VRE-BSI will lay the foundation for developing new therapeutic strategies that target antibiotic-resistant Gram-positive infections, which have high mortality and place a large burden on healthcare systems.
Please join us in congratulating Daria!