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Title: Streptomycin and Escherichia coli K12 MG1655 cell death
Author: Hough, Melinda Terace
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2008
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To investigate the molecular changes induced by streptomycin, spotted cDNA microarrays representing 99.6% of the E. coli K12 MG1655 genome were employed. Changes to the transcriptome were detected within 10-minutes of drug addition. Following 30-minutes of treatment, 172 transcripts representing 4% of the genome were differentially regulated; although rpsL, the molecular target of streptomycin, was not affected. A striking, and almost complete, induction of three key stress responses were observed: heat shock, phage shock, and drug sensitivity. Members of the heat shock response were most enriched; hsIS was consistently the highest up-regulated transcript. The most significant of the few uncharacterized transcripts observed was yccV, a hemi-methylated oriC DNA-binding protein. Surprisingly, a lack of coordination between the induction of the anaerobic metabolism transcriptional regulator, fnr, and its downstream targets was observed. Transcripts associated with the energy-rich processes of motility, chemotaxis, and anaerobic metabolism were repressed. To determine whether hsIS or yccV played a critical role in streptomycin-induced cell death, unmarked knock-out mutants were engineered and characterized. During mutant engineering, a previously undescribed large scar sequence was identified and sequenced. Neither mutant exhibited a reduction in fitness, change in the minimum inhibitory concentration, or dose-response when compared to the parent strain. These two targets may be important in the overall mechanism of streptomycin lethality, but are not solely responsible for it. The work presented herein provides a detailed picture of the immediate molecular response of E. coli K12 MG1655 to streptomycin and suggests that its antibiotic action as a whole is more complex than the interaction of a single compound with a single target.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available