Mechanisms of resistance to quinolones
TLDR
Resistance to fluoroquinolones typically arises as a result of alterations in the target enzymes and of changes in drug entry and efflux and can be mediated by plasmids that produce the Qnr protein, which protects the quinolone targets from inhibition.Abstract:
The increased use of fluoroquinolones has led to increasing resistance to these antimicrobials, with rates of resistance that vary by both organism and geographic region. Resistance to fluoroquinolones typically arises as a result of alterations in the target enzymes (DNA gyrase and topoisomerase IV) and of changes in drug entry and efflux. Mutations are selected first in the more susceptible target: DNA gyrase, in gram-negative bacteria, or topoisomerase IV, in gram-positive bacteria. Additional mutations in the next most susceptible target, as well as in genes controlling drug accumulation, augment resistance further, so that the most-resistant isolates have mutations in several genes. Resistance to quinolones can also be mediated by plasmids that produce the Qnr protein, which protects the quinolone targets from inhibition. Qnr plasmids have been found in the United States, Europe, and East Asia. Although Qnr by itself produces only low-level resistance, its presence facilitates the selection of higher-level resistance mutations, thus contributing to the alarming increase in resistance to quinolones.read more
Citations
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The Pervasive Effects of an Antibiotic on the Human Gut Microbiota, as Revealed by Deep 16S rRNA Sequencing
TL;DR: Ciprofloxacin treatment influenced the abundance of about a third of the bacterial taxa in the gut, decreasing the taxonomic richness, diversity, and evenness of the community, and support the hypothesis of functional redundancy in the human gut microbiota.
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Heavy use of prophylactic antibiotics in aquaculture: a growing problem for human and animal health and for the environment
TL;DR: Global efforts are needed to promote more judicious use of prophylactic antibiotics in aquaculture as accumulating evidence indicates that unrestricted use is detrimental to fish, terrestrial animals, and human health and the environment.
Journal ArticleDOI
Acquired Antibiotic Resistance Genes: An Overview
Angela H.A.M. van Hoek,Dik Mevius,Dik Mevius,Beatriz Guerra,Peter Mullany,Adam P. Roberts,Henk Aarts +6 more
TL;DR: Attention is paid to mobile genetic elements such as plasmids, transposons, and integrons, which are associated with AR genes, and involved in the dispersal of antimicrobial determinants between different bacteria.
Journal ArticleDOI
The worldwide emergence of plasmid-mediated quinolone resistance
TL;DR: Their insidious promotion of substantial resistance, their horizontal spread, and their co-selection with other resistance elements indicate that a more cautious approach to quinolone use and a reconsideration of clinical breakpoints are needed.
Journal ArticleDOI
Mechanism of quinolone action and resistance.
TL;DR: This review describes the development of the quinolones as antibacterials, the structure and function of gyrase and topoisomerase IV, and the mechanistic basis for quInolone action against their enzyme targets, and suggests approaches to designing new drugs that display improved activity against resistant strains.
References
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DNA gyrase, topoisomerase IV, and the 4-quinolones.
Karl Drlica,Xilin Zhao +1 more
TL;DR: Quinolone-topoisomerase biology is providing a model for understanding aspects of host-parasite interactions and providing ways to investigate manipulation of the bacterial chromosome by topoisomerases.
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Quinolone resistance from a transferable plasmid
TL;DR: Although resistance was low in wild-type strains, higher levels of quinolone resistance arose readily by mutation, suggesting that a multiresistance plasmid can speed the development and spread of resistance to these valuable antimicrobial agents.
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Antibiotic resistance among gram-negative bacilli in US intensive care units: implications for fluoroquinolone use.
Melinda M. Neuhauser,Robert A. Weinstein,Robert J. Rydman,Larry H. Danziger,George H. Karam,John P. Quinn +5 more
TL;DR: The increasing incidence of ciprofloxacin resistance among gram-negative bacilli that has occurred coincident with increased use of fluoroquinolones will be necessary to limit this downward trend.
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Mechanism of plasmid-mediated quinolone resistance
John H. Tran,George A. Jacoby +1 more
TL;DR: The cloned plasmid-quinolone resistance gene, termed qnr, was a 218-aa protein belonging to the pentapeptide repeat family and shared sequence homology with the immunity protein McbG, which is thought to protect DNA gyrase from the action of microcin B17, and the ability of Qnr to reverse the inhibition of gyrases activity by quinolones was tested.
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Resistance-Nodulation-Cell Division-Type Efflux Pump Involved in Aminoglycoside Resistance in Acinetobacter baumannii Strain BM4454
TL;DR: Insertional inactivation ofadeB in BM4454 showed that the corresponding protein was responsible for aminoglycoside resistance and was involved in the level of susceptibility to other drugs including fluoroquinolones, tetracyclines, chloramphenicol, erythromycin, trimethoprim, and ethidium bromide.