This item is under embargo and not available online per the author's request. For access information, please visit http://libanswers.wustl.edu/faq/5640.

Date of Award

Summer 8-15-2015

Author's School

Graduate School of Arts and Sciences

Author's Department

Biology & Biomedical Sciences (Molecular Genetics & Genomics)

Degree Name

Doctor of Philosophy (PhD)

Degree Type

Dissertation

Abstract

Antibiotic resistance genes from soil are ancient, diverse, and represent an evolutionary origin for resistance seen in the clinic. In my thesis, I demonstrate that the lateral exchange of antibiotic resistance genes has occurred between non-pathogenic soil bacteria and diverse human pathogens on recent timescales, indicating that the vast soil resistome may serve as a reservoir of resistance available to the clinic. Despite the apparent overlap between soil and clinical resistomes, factors that influence resistance gene composition in soil and their movement between genomes and habitats are largely unknown. To investigate these relationships, I performed functional metagenomic selections for antibiotic resistance genes from 18 grassland and agricultural soils, identifying 2895 resistance genes with sequences predominantly unlike those in public databases. I was able to identify factors that drive resistome composition across these soils, detecting strong correlations between resistance genes and (i) soil type, (ii) the amount of added nitrogenous fertilizer, and (iii) bacterial community composition. I also describe a novel family of tetracycline-inactivating enzymes, widespread in soil and with ties to pathogenic Legionella, but previously unrecognizable as antibiotic resistance genes. Because tetracycline inactivation is scarcely observed in hospitals, these enzymes may fill an empty niche in pathogenic organisms and should therefore be monitored for their dissemination potential into the clinic. Taken together, my data indicate that soil resistomes are largely structured by bacterial community composition, but are capable of exchanging resistance genes with clinical pathogens, including previously unseen resistance phenotypes. Further work to identify the ecological, taxonomic, and genetic risk factors associated with this resistance gene flow is warranted.

Language

English (en)

Chair and Committee

Gautam Dantas

Committee Members

Barak Cohen, Michael Brent, Jim Havranek, Scott Mangan, Himadri Pakrasi, Timothy Wencewicz

Comments

Permanent URL: https://doi.org/10.7936/K74T6GJ0

Available for download on Thursday, August 15, 2115

Included in

Biology Commons

Share

COinS