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Genomic analysis of bacterial resistance to narrow spectrum antibiotics : linking phenotypes to genotypes
Robert L. Dorit
Bachelor of Arts
Bacteriocins, Colicins, Antiobiotic resistance, Narrow-spectrum antibiotics, Sequencing
The discovery of antibiotics has drastically improved medical treatments and saved countless lives. Now, however, the spread and prevalence of microbial antibiotic resistance suggests that the golden age of antibiotics is coming to a halt due. The time has come for us to research alternatives to broad-spectrum antibiotics. This thesis seeks to investigate one such alternative: bacteriocins. Bacteriocins are proteinaceous toxins produced by nearly all bacteria and archaea, able to kill closely related strains through a variety of mechanisms, including the targeting of the cell membrane or cleavage of critical proteins, DNA, and RNA. We will be using colicins, bacteriocins produced by E. coli, as a model system. Beyond finding a viable alternative to the use of broad-spectrum antibiotics, there also remains a need to develop a more predictive theory of how antibiotic resistance will arise, in contrast to the largely retrospective work that has been done.
In this paper, we try to achieve a genetic analysis of bacterial resistance to narrow spectrum antibiotics through sequencing, to select for resistance in liquid and solid media, to examine the pathways of resistance through bioinformatic tools and phenotypic characterization, and to determine the costs of resistance through growth curves. We were able to select for resistance in both liquid and solid media, assess fitness costs and the presence of compensatory mutations through growth curves in both LB and minimal media, and perform multiple sequence alignments of known loci that are targeted by colicins to determine if there are selective pressures. Our current data helps establish methods to characterize the phenotypic and genotypic characteristics of resistance, and pave the way for future work of linking the phenotypic basis of resistance to underlying genotypes.
2020 Nancy Yoobin Jung. Access limited to the Smith College community and other researchers while on campus. Smith College community members also may access from off-campus using a Smith College log-in. Other off-campus researchers may request a copy through Interlibrary Loan for personal use.
Jung, Nancy Yoobin, "Genomic analysis of bacterial resistance to narrow spectrum antibiotics : linking phenotypes to genotypes" (2020). Honors Project, Smith College, Northampton, MA.
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53 pages : illustrations (chiefly color) Includes bibliographical references (pages 47-53)