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Towards an understanding of the mode of action of fluoroquinolone drugs

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Abstract

Fluoroquinolones are important antibacterial drags. They were found to interfere with the gyrase-DNA complex which causes cell death. However, the detailed mode of action on a molecular level is so far not understood.

In this contribution Raman spectroscopy is chosen as a non-invasive technique to first characterize the individual involved components: fluoroquinolone drags, and the biological targets DNA and gyrase; and second to study the influence of the fluoroquinolones on bacteria in in-vivo experiments.

The use of UV resonance Raman spectroscopy with excitation at 244 nm allows the investigation of the drags and the biological targets in aqueous solution at biological low concentrations (a few µM). Raman bands associated with the action of the enzyme gyrase could be identified in in-vitro mixing experiments. In-vivo experiments with bacteria experiencing varying drag concentrations revealed changes in the vibrational bands of the protein and DNA components within the bacterial cell caused by the action of the drag. Due to the complexity of the bacterial spectra advanced multivariate statistics in combination with variable selection methods proved to be useful in the data analysis.

© 2007 SPIE

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