QRDR

QRDR stands for Quinolone Resistance-Determining Region, a segment in the genes encoding the bacterial target enzymes DNA gyrase and topoisomerase IV. In most bacteria, the quinolone targets are DNA gyrase, a type II topoisomerase composed of GyrA and GyrB subunits, and topoisomerase IV, formed by ParC and ParE subunits. The QRDR lies within the N-terminal regions of GyrA and ParC and contains residues that directly interact with quinolones during catalysis. Mutations in the QRDR reduce drug binding and thereby decrease the drug's ability to stabilize the cleavage complex, leading to reduced susceptibility or resistance to quinolones and fluoroquinolones.

Mutational patterns are species dependent, but certain substitutions are commonly observed. In GyrA, mutations at residues corresponding to Ser83 and Asp87 in Escherichia coli are frequently associated with resistance; in ParC, substitutions at Ser80 and Glu84 are also commonly reported. Additional mutations in GyrB or ParE can contribute to higher levels of resistance. QRDR mutations often arise under selective pressure from quinolone therapy and may accumulate in a stepwise fashion, increasing minimum inhibitory concentrations.

Resistance may also involve plasmid-mediated mechanisms (such as qnr genes and aac(6')-Ib-cr), overexpression of efflux pumps, and reduced outer membrane permeability. The QRDR is a primary, but not sole, determinant of fluoroquinolone resistance.

Understanding QRDR is important for molecular surveillance of antibiotic resistance, interpretation of susceptibility tests, and informing treatment decisions in bacterial infections where fluoroquinolones are used.