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Department of Pharmacology

Houston, Texas

BCM students are involved in research.
Pharmacology
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Lynn Zechiedrich, Ph.D.

Photograph of Dr. Lynn Zecheidrich

Professor
Department of Molecular Virology and Microbiology

Department of Pharmacology
Department of Biochemistry and Molecular Biology

Kyle and Josephine Morrow Chair in Molecular Virology and Microbiology

elz@bcm.edu

Education

  • Ph.D. Vanderbilt University School of Medicine
  • Postdoctoral, University of California, Berkeley

Zechiedrich Lab web site

Fluoroquinolone Resistance in E. coli

Fluoroquinolones are among the most potent, widely prescribed, broad-spectrum oral antibiotics. Quinolones kill bacteria by targeting the two type-2 topoisomerases, gyrase and topoisomerase IV. These essential enzymes pass DNA strands through each other and are required for DNA replication, recombination, transcription, chromosome segregation, and maintenance of DNA supercoiling levels. Quinolones stabilize the normal, transient topoisomerase-DNA cleavage intermediate. With a mechanism that is not well understood, DNA tracking by processes such as replication or transcription collide with the drug-stabilized topoisomerase-DNA adducts to cause cell death.

To reach their cellular targets, drugs must first penetrate the defense system of the bacterial cell. Not only are cells well-equipped to withstand treatment with drugs, but it has become increasingly clear that bacteria undergo genetic alteration to become resistant to drugs. Although drug resistant bacteria are one of the most critical problems facing the medical community today, surprisingly little is known about how cells resist drugs. Therefore, the goal of our research is to determine how the model system Escherichia coli respond to and resist treatment with the quinolone antibiotics. Ultimately, our results may be used to design better chemotherapeutics to help prevent the worldwide problem of drug resistance.

DNA Topoisomerases, DNA Structure and DNA Topology

By passing DNA strands through each other, the ubiquitous topoisomerases control chromosome condensation, chromosome segregation, DNA replication, DNA transcription, and DNA recombination. Topoisomerases break and reseal DNA to modulate DNA supercoils, DNA catenanes, and DNA knots. Because of their essential roles, topoisomerases are the cellular targets for widely prescribed chemotherapeutics. The normally short-lived, broken DNA intermediate produced by topoisomerases is increased by the drugs, which causes cell death. We use biochemical, biophysical and genetic techniques to determine how topoisomerases carry out the cellular roles and how drugs block their function.

Learn more about Dr. Zechiedrich's work by visiting her lab home page.

For a complete list of Zechiedrich Lab publications please see both PubMed and Google Scholar.

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