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Exploring Synergy between Classic Mutagens and Antibiotics to Examine Mechanisms of Synergy and of Antibiotic Action

  • Author(s): Song, Yun
  • Advisor(s): Miller, Jeffrey H
  • et al.
Abstract

I used classical mutagens in Escherichia coli to study synergies with different classes of antibiotics, test models of antibiotic mechanisms of action, and examine the basis of synergy. The strongest synergies were detected with 4-nitroquinoline 1-oxide (4NQO), which oxidizes guanines and ultimately results in double-strand breaks when paired with the bactericidal antibiotics vancomycin (VAN), ciprofloxacin (CPR), trimethoprim (TMP), gentamicin (GEN), but no synergies with the bacteriostatic antibiotics tetracycline (TET), erythromycin (ERY), and chloramphenicol (CHL). Other mutagens tested display synergies with the bactericidal antibiotics to various degrees, also with some of the other mutagens. The results support models showing that bactericidal antibiotics kill bacteria by generating more double-strand breaks than can be repaired. The synergies represent dose effects of not the proximal target damage but rather the ultimate resulting double-strand breaks. I also used pairwise tests to place the mutagens into functional antibacterial categories within a previously defined drug interaction network.

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