PhD (Doctor of Philosophy)
Date of Award
Committee Chair or Co-Chairs
W. Scott Champney
Robert V. Schoborg, Mitchell E. Robinson, John J. Laffan, David A. Johnson
The bacterial ribosome is a target for inhibition by numerous antibiotics. Neomycin and paromomycin are aminoglycoside antibiotics that specifically stimulate the misreading of mRNA by binding to the decoding site of 16S rRNA in the 30S ribosomal subunit. Recent work has shown that both antibiotics also inhibit 30S subunit assembly in Escherichia coli and Staphylococcus aureus cells. This work describes the characteristics of an assembly intermediate produced in E.coli cells grown with neomycin or paromomycin. Antibiotic treatment stimulated the accumulation of a 30S assembly precursor with a sedimentation coefficient of 21S. The particle was able to bind radio labeled antibiotics both in vivo and in vitro. Hybridization experiments showed that the 21S precursor particle contained 16S and 17S rRNA. Ten 30S ribosomal proteins were found in the precursor after inhibition by each drug in vivo. In addition, cell free reconstitution assays generated a 21S particle during incubation with either aminoglycoside. Precursor formation was inhibited with increasing drug concentration. This work examines features of a novel antibiotic target for aminoglycoside and will provide information that is needed for the design of more effective antimicrobial agents.
Dissertation - unrestricted
Foster, Cerrone Renee, "Characterization of a 30S Ribsomal Subunit Intermediate Found in Escherichia coli Cells Growing with Neomycin and Paromomycin." (2007). Electronic Theses and Dissertations. Paper 2120. https://dc.etsu.edu/etd/2120
Copyright by the authors.