The introduction of quinolones, particularly ciprofloxacin, into clinical use in the 1980s led to widespread resistance in Enterobacteriaceae, often nonclonal. The primary mechanism of quinolone resistance involves mutations in bacterial enzymes targeted by quinolones, such as DNA gyrase and topoisomerase IV. However, the frequency of spontaneous double mutations is low, suggesting that horizontally transferable elements must also play a role. The discovery of qnr genes, which编码 plasmid-mediated quinolone resistance, has provided insights into this phenomenon. Qnr proteins protect DNA gyrase from quinolones and have been circulating for at least 20 years, achieving global distribution. Other mechanisms of quinolone resistance, such as AAC(6')-Ib-cr and quinolone extrusion, have also been found to be plasmid-borne. The discovery of qnr genes and the subsequent identification of various qnr variants have expanded our understanding of quinolone resistance. The mechanisms of action of Qnr proteins and related pentapeptide repeat proteins, such as MfpA and MebG, are discussed, along with their impact on quinolone MICs, mutant prevention concentrations, and in vivo activity. The coexistence of qnr with other resistance mechanisms and the potential for additive resistance is also explored. The origins of qnr genes and their potential aquatic reservoirs are considered, highlighting the rapid expansion of knowledge in this field.The introduction of quinolones, particularly ciprofloxacin, into clinical use in the 1980s led to widespread resistance in Enterobacteriaceae, often nonclonal. The primary mechanism of quinolone resistance involves mutations in bacterial enzymes targeted by quinolones, such as DNA gyrase and topoisomerase IV. However, the frequency of spontaneous double mutations is low, suggesting that horizontally transferable elements must also play a role. The discovery of qnr genes, which编码 plasmid-mediated quinolone resistance, has provided insights into this phenomenon. Qnr proteins protect DNA gyrase from quinolones and have been circulating for at least 20 years, achieving global distribution. Other mechanisms of quinolone resistance, such as AAC(6')-Ib-cr and quinolone extrusion, have also been found to be plasmid-borne. The discovery of qnr genes and the subsequent identification of various qnr variants have expanded our understanding of quinolone resistance. The mechanisms of action of Qnr proteins and related pentapeptide repeat proteins, such as MfpA and MebG, are discussed, along with their impact on quinolone MICs, mutant prevention concentrations, and in vivo activity. The coexistence of qnr with other resistance mechanisms and the potential for additive resistance is also explored. The origins of qnr genes and their potential aquatic reservoirs are considered, highlighting the rapid expansion of knowledge in this field.