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Chapter 25 : Plasmid-Mediated Quinolone Resistance

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Plasmid-Mediated Quinolone Resistance, Page 1 of 2

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Abstract:

Plasmid-mediated quinolone resistance (PMQR) was late in being discovered. Nalidixic acid, the first quinolone to be used clinically, was introduced in 1967 for urinary tract infections. Resistance was soon observed and could also be readily selected in the laboratory. It was produced by amino acid substitutions in the cellular targets of quinolone action: DNA gyrase and topoisomerase IV ( ). Later, decreased quinolone accumulation due to pump activation and porin loss was added as an additional resistance mechanism. The search for transferable nalidixic acid resistance in over 500 Gram-negative strains in the 1970s was unrevealing ( ). In the 1980s fluoroquinolones became available that were more potent and broader in spectrum. Quinolone usage increased, with subsequent parallel increases in quinolone resistance ( ). In 1987 PMQR was reported to be present in a nalidixic acid-resistant isolate of from Bangladesh ( ), but this claim was later withdrawn ( ). True PMQR was reported in 1998 in a multiresistant urinary isolate at the University of Alabama that could transfer low-level resistance to nalidixic acid, ciprofloxacin, and other quinolones to a variety of Gram-negative recipients ( ). The responsible gene was termed , later amended to as additional alleles were discovered. Investigation of a plasmid from Shanghai that provided more than the expected level of ciprofloxacin resistance led to the discovery in 2006 of a second mechanism for PMQR: modification of certain quinolones by a particular aminoglycoside acetyltransferase, AAC(6′)-Ib-cr ( ). A third mechanism for PMQR was added in 2007 with the discovery of plasmid-mediated quinolone efflux pumps QepA ( ) and OqxAB ( ). A multiplex PCR assay for eight PMQR genes (lacking only ) has recently been perfected ( ). In the past decade these genes have been found in bacterial isolates from around the world. They reduce the susceptibility of bacteria to quinolones, usually not to the level of nonsusceptibility but facilitating the selection of more quinolone-resistant mutants and treatment failure. PMQR has been frequently reviewed ( ).

Citation: Jacoby G, Strahilevitz J, Hooper D. 2015. Plasmid-Mediated Quinolone Resistance, p 475-503. In Tolmasky M, Alonso J (ed), Plasmids: Biology and Impact in Biotechnology and Discovery. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.PLAS-0006-2013

Key Concept Ranking

Mobile Genetic Elements
0.59712535
Transcription Start Site
0.51740056
DNA Topoisomerase IV
0.41384226
Genetic Elements
0.41092497
Urinary Tract Infections
0.40523073
0.59712535
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Figures

Image of Figure 1
Figure 1

The rod-like structure of the QnrB1 dimer is shown above, with the sequence of the monomer below. The sequence is divided into four columns representing the four faces of the right-handed quadrilateral β-helix. Face names and color are shown at the top along with the naming convention for the five residues of the pentapeptide repeats. Loops A and B are indicated by one and two asterisks, respectively, with their sequences indicated below and the loops shown as black traces on the diagram. The N-terminal α-helix is colored pink. The molecular 2-fold symmetry is indicated with a black diamond. Type II turn-containing faces are shown as spheres, and type IV-containing faces as strands ( ). Adapted from the ( ), copyright 2011, the American Society for Biochemistry and Molecular Biology. doi:10.1128/microbiolspec.PLAS-0006-2013.f1

Citation: Jacoby G, Strahilevitz J, Hooper D. 2015. Plasmid-Mediated Quinolone Resistance, p 475-503. In Tolmasky M, Alonso J (ed), Plasmids: Biology and Impact in Biotechnology and Discovery. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.PLAS-0006-2013
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Image of Figure 2
Figure 2

QnrB1 protection of DNA gyrase from ciprofloxacin inhibition of supercoiling. Reaction mixtures of 30 µl were analyzed by agarose gel electrophoresis. Reaction mixtures contained 0.2 µg relaxed pBR322 DNA (lanes 1 to 14), 6.7 nM gyrase (lanes 2 to 14), 2 µg/ml ciprofloxacin (lanes 3 to 14), and QnrB-His6 fusion protein at 25 µM (lane 4), 5 µM (lane 5), 2.5 µM (lane 6), 0.5 µM (lane 7), 50 nM (lane 8), 5 nM (lane 9), 0.5 nM (lane 10), 50 pM (lane 11), 5 pM (lane 12), or 0.5 pM (lane 13). Reprinted from reference . doi:10.1128/microbiolspec.PLAS-0006-2013.f2

Citation: Jacoby G, Strahilevitz J, Hooper D. 2015. Plasmid-Mediated Quinolone Resistance, p 475-503. In Tolmasky M, Alonso J (ed), Plasmids: Biology and Impact in Biotechnology and Discovery. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.PLAS-0006-2013
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Image of Figure 3a
Figure 3a

Genetic environment of alleles. doi:10.1128/microbiolspec.PLAS-0006-2013.f3a

Citation: Jacoby G, Strahilevitz J, Hooper D. 2015. Plasmid-Mediated Quinolone Resistance, p 475-503. In Tolmasky M, Alonso J (ed), Plasmids: Biology and Impact in Biotechnology and Discovery. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.PLAS-0006-2013
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Image of Figure 3b
Figure 3b

Genetic environment of alleles. doi:10.1128/microbiolspec.PLAS-0006-2013.f3b

Citation: Jacoby G, Strahilevitz J, Hooper D. 2015. Plasmid-Mediated Quinolone Resistance, p 475-503. In Tolmasky M, Alonso J (ed), Plasmids: Biology and Impact in Biotechnology and Discovery. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.PLAS-0006-2013
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Image of Figure 3c
Figure 3c

Genetic environment of alleles. doi:10.1128/microbiolspec.PLAS-0006-2013.f3c

Citation: Jacoby G, Strahilevitz J, Hooper D. 2015. Plasmid-Mediated Quinolone Resistance, p 475-503. In Tolmasky M, Alonso J (ed), Plasmids: Biology and Impact in Biotechnology and Discovery. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.PLAS-0006-2013
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Image of Figure 4
Figure 4

Survival at increasing fluoroquinolone concentrations for J53 and J53 pMG252. A large inoculum (10 colony forming units) and appropriate dilutions were applied to Mueller-Hinton agar plates containing the indicated concentration of ciprofloxacin, and surviving colonies were counted after incubation for 72 h at 37°C. doi:10.1128/microbiolspec.PLAS-0006-2013.f4

Citation: Jacoby G, Strahilevitz J, Hooper D. 2015. Plasmid-Mediated Quinolone Resistance, p 475-503. In Tolmasky M, Alonso J (ed), Plasmids: Biology and Impact in Biotechnology and Discovery. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.PLAS-0006-2013
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