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Date of Award
Doctor of Philosophy (PhD)
Xenobiotic compounds are any chemicals that are released into an environment by human action and that occur at concentrations higher than found naturally. Xenobiotics, including aromatic compounds and antibiotics, are recalcitrant to degradation because they are often toxic or mutagenic. Despite this toxicity, bacteria account for a large portion of xenobiotic degradation in the environment. Bacteria are able to adapt to these foreign chemicals, gaining increased levels of tolerance and increased rates of xenobiotic degradation. On the strain level, increased tolerance can be caused by mutations in individual cells or through the acquisition of genes from other cells. At the community level, xenobiotics select for naturally resistant bacterial often resulting in an increase in genes involved with xenobiotic tolerance. The goal of my thesis was to (1) understand how bacterial strains evolve increased tolerance to toxic aromatics xenobiotics through adapted evolution and (2) how microbial communities in mammalian guts are altered due to xenobiotic selection pressure. To determine the microbial adaptations that occur in bacterial strains exposed to xenobiotics, I studied the changes that occurred in the genome and transcriptome of Rhodococcus opacus PD630 when grown over several generations on increasing concentrations of toxic aromatic compounds. Chemical pretreatment of lignocellulose as a first step in biofuel production results in the creation of monomeric sugars and toxic xenobiotic compounds. Bacterial conversion of the resulting moiety to biofuel precursors is one of the most cost-effective methods of biofuel production. However, the toxic aromatic compounds created from lignocellulose pretreatment inhibit bacterial growth and reduce overall productivity. R. opacus is a bacterial strain that naturally has a high tolerance to aromatic compounds and optimization of this bacteria can improve process efficiency. By analyzing 35 R. opacus strains adapted on 6 different compounds or compound mixtures, I show that adapted strains demonstrated up to 1900% improvement in final cell densities. I found no mutations in xenobiotic degradations genes for the adapted strains, but I found several mutations in genes that are involved with oxidation-reduction reactions that may assist in degradation. These results demonstrate that bacterial strains can gain increased xenobiotic tolerance by fine-tuning metabolic pathways indirectly related to xenobiotic degradation. To determine the effects of xenobiotic selection on microbial communities, I studied the gut microbiome of humans, captive chimpanzees, and captive gorillas that have received antibiotic treatment compared to the microbiome of wild chimpanzees and gorillas that have never received antibiotic treatment. I found that antibiotic treatment was correlated with higher richness and abundance of antibiotic resistance genes. In addition, the microbiome and resistome in captive apes were more similar to that of humans than to the wild apes, despite differences in host species and large geographic distances between the human and captive apes. Together, these results suggest that host lifestyle, including diet and antibiotic treatment, is more influential in microbiome composition than host species and geographic proximity. I also identified a number of novel antibiotic resistance genes for which further investigation is warranted.
Chair and Committee
Arpita Bose, Andrew Kau, Audrey Odom-John, Himadri Pakrasi,
Campbell, Tayte Paul, "Multi-omic Understanding of the Evolution of Xenobiotic Tolerance in Bacterial Isolates and Communities" (2019). Arts & Sciences Electronic Theses and Dissertations. 1888.
Available for download on Wednesday, November 04, 2020