Synergistic Use of Exo VII Inhibitors And Quinolone Antibiotics For Treating Bacterial Infection

Technology Bundle IDNCI-E-171-2020 Synergistic Use of Exo VII Inhibitors And Quinolone Antibiotics For Treating Bacterial InfectionApplicationsTherapeuticsLead InventorsShar-yin Huang (NCI)Yves Pommier (NCI)Co-InventorsBrianna Mitchell (NCI)Development StatusPre-clinical (in vivo)ICsNCITopoisomerase poisons, such as quinolone antibiotics, are widely used as anticancer drugs and antibiotics. Quinolone antibiotics act by trapping prokaryotic type IIA topoisomerases (DNA gyrase and TOPO IV), resulting in irreversible topoisomerase cleavage complexes. However, current U.S. Food and Drug Administration (FDA) guidance reserves the use of quinolones for the most serious bacterial infections due to their associated side effects and to limit the occurrence of drug-resistant bacterial strains. Resistance to available antibiotics in pathogenic bacteria is a global challenge as the number of drug-resistant strains increased dramatically each year.  Combination of antibiotics with antibiotic adjuvants offers a productive strategy to address the widespread emergence of antibiotic-resistant strains. Exonuclease VII (ExoVII) repairs quinolone-induced DNA damage by excising the tyrosyl-DNA linkage between DNA and trapped DNA gyrase, an essential prokaryotic type II A topoisomerase. Consequently, inactivation of ExoVII results in hypersensitivity to quinolones. Researchers at the NCI have discovered ExoVII inhibitors that synergize with the antimicrobial activity of the quinolone antibiotic ...
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