Advancing Analytical Methods for Investigating the Epidemiology of Antimicrobial Resistance using Campylobacter coli from Swine Populations as a Model System

PROJECT SUMMARY/ABSTRACT
The emergence and persistence of antimicrobial resistant pathogens are a serious threat to human and animal
populations worldwide. Although antimicrobial use is known to select for antimicrobial resistance (AMR),
resistance often persists in the absence of antimicrobial exposure. An improved understanding of the
epidemiology of AMR in natural pathogen populations is needed. However, traditional epidemiological methods
are not well-suited for understanding AMR risk factors because they do not account for the ecological and
evolutionary processes that confound the expected association between antimicrobial exposure and AMR.
Improved epidemiological methods that incorporate ecological and evolutionary principles are necessary for
providing new insights on AMR, informing more effective AMR prevention strategies, and ultimately promoting
the future efficacy of antimicrobial therapies. The long-term goal of this research is to develop a quantitative
framework integrating ecological and evolutionary principles with epidemiological methods to advance existing
knowledge of AMR risk among human and animal populations. This proposal aims to use commensal
Campylobacter coli populations in commercial swine herds as a model system to investigate the ecology,
evolution, and epidemiology of AMR. Prior studies found that C. coli from pigs reared under both conventional
and antibiotic-free farms were resistant to fluoroquinolone and macrolide antibiotics, which is clinically significant
as these drugs are used to treat human campylobacteriosis. The proposed research will build upon this previous
work and accomplish the following aims: 1) identify and quantify host exposures and microbial genotypes
associated with phenotypic resistance to fluoroquinolone and macrolide drugs among commensal C. coli in swine
herds using probabilistic graphical models (i.e. chain graphs), and 2) quantify selection and bacterial fitness
costs of genotypes associated with fluoroquinolone- and macrolide-resistance among natural C. coli populations
in presence and absence of antimicrobial use, using phylodynamic methods. The expected outcome of this
research is the development of a quantitative framework that can be applied to any host-pathogen system in
which AMR is a threat to elucidate drivers of AMR selection and persistence. This proposal and mentorship team
will provide training critical for the applicant’s development as an independent clinician-scientist studying
infectious disease epidemiology at the human-animal interface. The interdisciplinary research training plan will
provide the applicant opportunities to develop skills in molecular epidemiology, computational biology and
infectious disease epidemiology. The comparative clinical training plan will enable the applicant to gain
experience in infectious disease management among both human and animal populations under the guidance
of infectious disease physicians and veterinary epidemiologists. The training environment at North Carolina State
University is ideal for the applicants cross-disciplinary training goals, as the applicant also has access to
resources and opportunities at Duke University and University of North Carolina-Chapel Hill.