Suppression of the sos response reverses antimicrobial resistance across a range of e. Mechanisms of resistance to the quinolones have been described for several bacterial species, but mainly for escherichia coli and staphylococcus aureus. The articles in the ebook update the reader on various aspects and mechanisms of antibiotic resistance. Quinolone and fluoroquinolone antibiotics are potent, broadspectrum agents commonly used to treat a range of infections. As is the case with other antibacterial agents, the rise in quinolone resistance threatens the clinical utility of this important drug class. The reported fq resistance mechanisms in gramnegative bacteria include mutation or downexpression of quinoloneentrance porins, mutations in dna gyrase andor topoisomerase iv. Mechanism of quinolone action and resistance semantic. Mechanisms of quinolone resistance in clinical isolates of. Pdf quinolone antimicrobials are synthetic and widely used in clinical medicine. Principal mechanisms of bacterial resistance to quinolones are modification of target enzymes, dna gyrase gyra and topoisomerase iv parc, or reduction of intracellular concentration due to mutations in the regulatory genes for efflux systems, such as mexr and nfxb.
Quinolone resistance reversion by targeting the sos response. Resistance to quinolones quinolone resistance has multiple mechanisms and significant clinical impact. Jacoby 2,3 1 division of infectious diseases, massachusetts general hospital, boston, massachusetts. Frontiers mechanisms of antibiotic resistance microbiology. However, mechanisms of resistance at the molecular level are not yet entirely elucidated. Given their synthetic origin, it was early proposed that the mechanisms of resistance to quinolones would not include the acquisition of resistance genes through horizontal gene transfer and should be mainly due to mutations in the genes encoding their targets and eventually in the transporters of the antimicrobials. Mechanisms of resistance to quinolones springerlink. Additional mutations in the next most susceptible target, as well as in genes controlling drug accumulation, augment resistance further, so that the. Mechanisms of resistance include two categories of mutation and acquisition of resistanceconferring. Quinolone antimicrobials are synthetic and widely used in clinical medicine. Mechanisms of action and resistance of older and newer.
The first plasmidmediated quinolone resistance gene, qnra1, was detected in 1998. Resistance to these agents is multifactorial and can be via one or a combination of targetsite gene mutations, increased production of multidrugresistance mdr efflux pumps, modifying enzymes, andor targetprotection proteins. The continued development and testing of newer fluoroquinolones have provided a better understanding of the mechanisms of action and resistance in this class. Resistance emerged with clinical use and became common in some bacterial pathogens. Mechanism of quinolone action and resistance biochemistry. Mutations on the target enzymes usually cause resistance to quinolones specifically, but mutations affecting drug accumulation confer. Quinolone resistance due to mutation in chromosomal genes. Piddock,y school of immunity and infection, institute of microbiology and infection, biosciences building, university road west, university. This section describes common antibiotic resistance mechanisms in bacteria. Thus the mechanisms of 4quinoloneresistance in these mrsa isolates involved alterations in both dna gyrase and antimicrobial uptake and efflux.
The mutational landscape of quinolone resistance in escherichia coli. However, other mechanisms such as mutations that lead to reduced intracellular drug concentrations, by either decreased uptake or increased efflux, and plasmidencoded resistance genes producing either target protection proteins, drugmodifying enzymes or multidrug efflux pumps are known to contribute additively to quinolone resistance. Broad use of fluoroquinolones has been followed by emergence of resistance, which has been due mainly to chromosomal mutations in genes encoding the subunits of the drugs target enzymes, dna gyrase and topoisomerase iv, and in genes that affect the expression of diffusion channels in the outer membrane and multidrugresistance efflux systems. Full text quinolone resistance mechanisms among third. No specific quinolonemodifying or degrading enzymes have been found. Resistance emerged with clinical use and became common. Three mechanisms of resistance to quinolones are currently recognized. The targets of quinolone action are the essential bacterial enzymes dna gyrase and dna topoisomerase iv. Here we report the cloning of qnr, the novel plasmidencoded.
Transferable mechanisms of quinolone resistance from 1998. Initial studies of resistant clinical isolates of staphylococcus aureus prior to the recognition of the role of topoisomerase iv in resistance commonly had gyra mutations, but when parc and pare were also evaluated, gyra quinolone resistance mutations were not found in the absence of mutations in topoisomerase iv. Resistance mechanisms cag annals of translational medicine. The aim of this study was to determine the plasmid and chromosomal mechanisms of quinolone resistance in enterobacter isolates resistant to thirdgeneration cephalosporins from the university hospital saint marina varna, bulgaria, as well as to assess their association with esblampc presence and plasmid replicon types. This in turn either kills the bacteria or stops them from multiplying. The results of this study show that reduced fluoroquinolone susceptibility among foreign s. Currently, 2 different mechanisms are considered to be major determinants of fluoroquinolone resistance. Mechanisms of resistance to quinolones oxford academic journals. Mechanisms of action and of resistance to quinolones. Resistance to quinolones is increasing worldwide, but is still relatively infrequent among anaerobes. A better understanding of these mechanisms should facilitate the development of means to potentiate the efficacy and increase the lifespan of antibiotics while minimizing the emergence of. Resistance to quinolones can also be mediated by plasmids that produce the qnr protein. Resistance mutations in one or both of the two drug target enzymes, dna gyrase and dna topoisomerase iv.
The use of the quinolone antibiotic enrofloxacin in swine herds appears to have promoted ciprofloxacin resistance. Recently, a multiresistance plasmid was discovered that encodes transferable resistance to quinolones. Antibiotic resistance is one of the most pressing global concerns in medicine, with highly resistant pathogens of many. Plasmidmediated quinolone resistance mechanisms have also been described 7. Antibiotic resistance became a global health threat. Mechanisms of 4quinolone resistance in quinoloneresistant and methicillinresistant staphylococcus aureus isolates from japan and. Antibiotics disrupt essential structures or processes in bacteria. Read mechanisms of quinolone resistance in clinical isolates of enterobacter cloacae, clinical microbiology and infection on deepdyve, the largest online rental service for scholarly research with thousands of academic publications available at your fingertips. Antibiotic resistance mechanisms focusing on quinolones. Also the in vitro activity of azithromycin was determined, with the aim to find an alternative for the fluoroquinolone treatment of salmonellosis. We have cloned the plasmidquinolone resistance gene, termed qnr, and found it in an integronlike environment upstream from qace.
Because of the wide use and overuse of these drugs, the number of quinoloneresistant bacterial strains has been growing steadily since the 1990s. Although there is evidence that restricted use of a specific antibiotic can be followed by a decrease in drug resistance to that agent, drug resistance control is. Previous studies have shown that quinolone resistance arises by mutations in chromosomal genes. In 1998, the first tmqr was soundly described, that is, qnra. Mechanisms of resistance to quinolones clinical infectious. Mechanisms of fluoroquinolone resistance in all species studied, mechanisms of fluoroquinolone resistance include one or two of the three main mechanistic categories, alterations in the drug target, and alterations in the permeation of the drug to reach its target.
Clinical and epidemiological aspects, is devoted to the clinical aspects of drug resistance. We have examined gyra, parc, mexr, and nfxb genes from 16 quinoloneresistant clinical isolates of pseudomonas aeruginosa to. Porin and efflux mechanisms are frequent companions of multiple drug resistance in acinetobacter and p. As discussed above, the vast majority of clinically relevant mutations cause quinolone resistance through a common mechanism, namely by disrupting the watermetal ion bridge. Mechanisms of quinolone resistance mechanism gene alteration effector genes species other factors altered target with reduced drug binding mutation in chromosomal structural genes. Additional mutations in the next most susceptible target, as well as in genes controlling drug accumulation, augment resistance further, so that the mostresistant isolates have mutations in several genes.
Mechanisms of resistance the major resistance mechanisms of microbes are decreased drug uptake, efflux pumps, enzymes that inactivate an antimicrobial chemical and target alterations by mutation. Emerging mechanisms of fluoroquinolone resistance volume. Drug resistance antimicrobial resistance is the reduction in effectiveness of a drug in curing a disease. Two main mechanisms, alteration of target enzymes gyrase and topoisomerase iv caused by chromosomal mutations in encoding genes, or reduced intracellular accumulation due to increased efflux of the drug, are associated with quinolone resistance. Such mutations include the mara locus inescherichia coli and result in low level resistance towards quinolones and unrelated drugs. Further overall structural developments resulted in 3rdgeneration drugs such as levofloxacin levo. Bacteria have in turn evolved many antibiotic resistance mechanisms to withstand the actions of antibiotics. As mentioned, plasmids are now known to mediate quinolone resistance, indicating a new array for fundamental research and clinical consideration. The main resistance mechanism consists of one or a combination of targetsite gene mutations that alter the drugbinding affinity of target enzymes. When the drug is not intended to kill or inhibit a pathogen, then the term is equivalent to dosage failure or drug tolerance. Antibiotic resistance is the ability of bacteria to resist the effect of an. With the exception of plasmidmediated quinolone resistance discussed later, acquired quinolone resistance by altered drug permeation occurs largely by mutations in genes encoding regulatory proteins that control the transcription of efflux pump or porin genes grkovic et al. The volumes included in antimicrobial drug resistance represent the first comprehensive, multidisciplinary reference covering the area of antimicrobial drug resistance in bacteria, fungi, viruses, and parasites from basic science, clinical, and epidemiological perspectives the first volume, antimicrobial drug resistance, mechanisms of drug resistance, is dedicated to the biological basis of. Meaning of drug resistance mechanisms of drug resistance origin of drug resistance transmission of drug resistance drugresistance encounter 1.
Fq resistance is emerging with clinical use and becoming common in some bacterial pathogens. Mechanisms of resistance include two categories of mutation and acquisition of resistance. It should be noted that higher levels of quinolone resistance are seen if a plasmid or strain carries two or more genes for quinolone resistance, such as both qnr and aac6. Mechanisms of quinolone resistance in clinical strains of. Mechanisms of resistance include two categories of mutation and acquisition of resistanceconferring genes. Resistance emerged with clinical use and became common in. Quinolone resistance is induced by mutations on quinolone target enzymes such as gyrase and topo iv, and by mutations that prevent drug accumulation as a result of changes in outer membrane proteins andor activation of drugefflux pumps.
843 618 923 633 1217 27 1200 1300 339 627 91 1399 1507 265 612 518 1134 956 1202 1297 1419 999 1325 1393 1162 202 1056 895 1226 1416 279 238 336 381 66 905 340 881 679 695 1349 673 643 539 1371 921 418 807 520 1001 1156