April 10, 2020 - 12:30 PM to 1:30 PM
“Genetic Capitalism and Stabilizing Selection of Antimicrobial Resistance Genes in Escherichia coli” - Dan Janies, Ph.D. (Carol Grotnes Belk Distinguished Professor of Bioinformatics and Genomics)
Antimicrobial resistance (AMR) in pathogenic strains of bacteria, such as Escherichia coli (E. coli), adversely impact personal and public health. In this study, we examine competing hypotheses for the evolution of AMR including: 1) ``genetic capitalism'' in which genotypes that confer antibiotic resistance are gained and not often lost in lineages, and 2) ``stabilizing selection'' in which genotypes that confer antibiotic resistance are gained and lost often. To test these hypotheses, we assembled a dataset that includes annotations for 409 AMR genotypes and a phylogenotypetic tree based on genome-wide single nucleotide polymorphisms from 29,255 isolates of E. coli. We used phylogenetic methods to count the times each AMR genotype was gained and lost across the tree and clustered the genotypes with respect to their gain and loss rates. We demonstrate that many genotypes cluster to support the hypothesis for genetic capitalism while a few cluster to support the hypothesis for stabilizing selection. Comparing the sets of genotypes that fall under each of the hypotheses, we found a statistically significant difference in the breakdown of resistance mechanisms through which the AMR genotypes function. The result that many AMR genotypes cluster under genetic capitalism, reflects that strong positive selective forces, primarily induced by human industrialization of antibiotics, outweigh the potential fitness costs to the bacterial lineages for carrying the AMR genotypes. We expect genetic capitalism to further drive bacterial lineages to resist antibiotics. We find that antibiotics that function via replacement and efflux tend to behave under stabilizing selection and thus may be valuable in an antibiotic cycling strategy.
In 2012, Daniel Janies joined the faculty of the University of North Carolina at Charlotte as The Carol Grotnes Belk Distinguished Professor of Bioinformatics and Genomics and co-Director of Bioinformatics Research. He is also the co- director of the Ribarsky Center for Visual Analytics. Dr. Janies received a Bachelor of Sciences degree in Biology from the University of Michigan in 1988 and a Ph.D. in Zoology from the University of Florida in 1995. Dr. Janies worked as a postdoctoral fellow (1996 - 1999) and a principal investigator (2000-2002) at the American Museum of Natural History in New York City where he led a team that, using off-the-shelf PC components, built one of the worlds largest computing clusters in 2001. Most recently, Dr. Janies was a tenured faculty member in the College of Medicine at the Ohio State University. Dr. Janies has served as a national principal investigator in the Tree of Life program of the National Science Foundation. Dr. Janies awards include DoD sponsored work to develop visual analytic applications to understand the spread of pathogens. He has developed the theory and practice of mapping pathogen genetic data in concert with geography and host animals. His results are akin to weather maps for infectious diseases that allow public health scientists to visualize when and where pathogens jump from animals to humans and evolve to resist drugs. Dr. Janies has advised the White House, the Pentagon, the USG Interagency Risk Assessment Consortium, and testified to both Houses of Congress on emerging infectious diseases.
The talk is based on the joint work with Colby T. Ford, Gabriel Lopez Zenarosa, Kevin Smith, David Brown, and John Williams
Organizer: Min Shin