The past decade has witnessed a dramatic increase in Staphylococcus aureus infections acquired from the community. Yet there remains a limited understanding of how these strains spread and subsequently become established and persist within communities. Our research is focused on identifying molecular mechanisms that allow epidemic S. aureus strains such as USA300 to successfully disseminate. This project uses a combined approach of whole-genome comparative sequencing of longitudinally collected samples, genetic manipulation, and functional studies on bacterial adhesion and survival. These molecular studies are informed by ongoing epidemiological studies on S. aureus transmission in the local community. This work has identified a potentially newly emerging S. aureus strain, ST398, which was previously only associated with close contacts to animals. Ongoing studies are aimed at elucidating the molecular mechanisms of its cross-species transfer and current animal-independent spread.
Klebsiella Pneumoniae Infections in Transplant Patients
Infections with carbapenem-resistant Enterobacteriaceae (CRE) have emerged as an urgent threat to healthcare, the “category of highest concern” in the 2013 CDC antimicrobial threat report. These multi-drug resistant infections are associated with high mortality. Recipients of solid organ transplantation, in particular liver transplant recipients are at increased risk for CRE infections. While intestinal colonization with CREs has been proposed as a potential risk factor for infections during CRE outbreaks, its actual contribution to infection remains incompletely understood. Moreover, there is a fundamental gap in knowledge on how these antibiotic resistant organisms transition from colonization to infection within affected hosts. We have established a cohort study of patients undergoing liver transplantation in which we aim to investigate the contribution of colonization to subsequent CRE infection. The long-term goal of this project is to elucidate at the bacterial genome level how CRE infections emerge and spread. Understanding these processes is critical to developing intervention and real-time clinical monitoring approaches to limit the impact of CRE infections at an individual and population level.
Microbiome in Infectious Diseases
During intestinal colonization, microorganisms closely interact with their surrounding bacterial communities and the immune system. Even single doses of antibiotics can profoundly affect the composition of the gut microbiota. The effects of organ transplantation on the microbiome are multifaceted, including the underlying disease, immunosuppressants, perioperative antibiotics, and the surgery itself. We are investigating how the intestinal microbiome modulates colonization with multi-drug resistant organisms in liver transplant recipients. Additional studies focus on the interaction of the intestinal and oral gut microbiome with the immune system in persons living with HIV.