Date of Award

Spring 1991

Degree Type

Thesis - Restricted

Degree Name

Master of Science (MS)




The concept of a topologically active DNA molecule, as opposed to a static Watson and Crick double helix, emerged in the mid 1960's and since then researchers have attempted to elucidate the function that topological changes might have for DNA. An essential enzyme in this topological activity is deoxyribonucleic acid topoisomerase II or "gyrase" as it is referred to in eubacteria and archaebacteria. Gyrase has been focused on not only because of its genetic regulation, but also because of its interaction with several groups of antibiotics, one of these being the quinolone family of antibiotics. The newer fluoroquinolones, such as ciprofloxacin, norfloxacin, and enoxacin, exhibit improved antimicrobial activity, however activity against gram-positive bacteria such as streptococci is still considerably less than that observed for gram-negative bacteria. Streptococcal strains, and Streptococcus pyogenes in particular, consistently have been shown to exhibit the highest MICs to these drugs. For these reasons I feel that S. pyogenes would make an appropriate choice of gram-positive eubacteria from which to find a functional gyrase A subunit gene whose gene product interacts differently with quinolones, and hence may possess additional or different functional domains. With functionally different gyrase subunit A genes available for analysis, it will be possible to analyze function-to domain relationships of the A subunit and its interactions with the B subunit.