Antibiotic resistance has been recognized by the World Health Organization as one of the three major threats to
human health. Multi-drug resistant organisms (MDR) such as carbapenem-resistant Enterobacteriaceae (CRE)
are associated with high morbidity and mortality. Novel approaches are needed to limit the emergence of MDR
bacteria, track and prevent their spread, and implement innovative strategies to eliminate them from colonizing
niches. Recent advances in next-generation sequencing afford an unprecedented opportunity to simultaneously
obtain information on the genomic make-up of infectious isolates and their mechanisms of drug resistance and
virulence and identify pathogen transmission within health-care facilities. Moreover, we are only now beginning
to understand the contribution of the microbiota to human health through 16S rRNA sequencing. My Mentoring
Program will train the next generation of Infectious Diseases clinicians, researchers and clinical microbiologists
in leveraging the rich genomic information into patient-oriented research (POR) and clinical decision-making.
In my program, trainees will be mentored through research projects, individual meetings and didactics to address
how antimicrobial resistance spreads and evolves. I outline three major areas of research in my laboratory, which
form the basis for potential projects for my mentees. These serve as examples of the different research directions
trainees can pursue. Core projects focus on metagenomic features of gut colonization and clearance of MDROs,
progression to systemic or urinary tract infections (Aims 1 and 4), and how these are affected by antibiotic
treatment. Results will provide building blocks for clinical management of MDR colonization that is informed by
the gut microbiome, such as future diagnostic and therapeutic targets. For Aim 2, we will study the contribution
of the gut microbiome to non-infectious complications of liver transplantation, specifically acute cellular rejection.
These projects illustrate how the resources I built will empower research by trainees and fellows from different
disciplines and with distinct scientific interests. We will take advantage of innovative tools developed in my lab,
including long-read sequencing and metagenomics. My mentoring program will provide trainees with the skills
needed to articulate their own research directions in antimicrobial drug resistance, molecular epidemiology, or
hospital epidemiology. Trained mentees will be in a position to apply novel approaches to study the evolution of
drug resistance and explore how intestinal microbial communities contribute to pathogen colonization and long-
term non-infectious complications such as allograft rejection in liver transplant patients. Through these studies
they will publish scholarly work and obtain grant support, thus launching them on the path to independence. I
will serve as the primary mentor for each trainee. The program will combine my strong personal commitment to
creating effective mentoring relationships with a comprehensive institutional program of training for young
investigators. This research has direct translational impact in establishing a framework to track the emergence
of MDROs that will inform novel diagnostic and therapeutic containment strategies.