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Chapter 65 : Mechanisms of Quinolone Resistance

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Mechanisms of Quinolone Resistance, Page 1 of 2

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Abstract:

With the increasing use of quinolones for the treatment of gram-positive bacterial infections, an understanding of the mechanisms of quinolone resistance in gram-positive bacteria is of considerable importance. This chapter summarizes the current understanding of established mechanisms of resistance to this class of antimicrobial agents in gram-positive bacteria. There are important differences between gram-positive and gram negative bacteria both in target enzyme sensitivity and in the means by which efflux resistance mechanisms operate that are of clinical and fundamental importance. Quinolones interact with both of the two type 2 topoisomerases in eubacteria, DNA gyrase and topoisomerase IV, which are essential for bacterial DNA replication. Quinolone-resistant clinical and laboratory strains of have been shown to have reduced accumulation of quinolones that is reversible with reserpine, suggesting the involvement of an efflux system(s) in quinolone resistance. Quinolone-resistant clinical isolates of viridans streptococci have been shown to have an efflux phenotype defined as lower MICs of quinolones in the presence of reserpine. DNA from such strains of and was able to transform to efflux phenotype in the laboratory. Overexpression of and genes for topoisomerases from plasmids are known, however, to have toxic effects on the cell that may limit the fitness of resistant bacteria containing them. Thus, at present quinolone resistance in gram-positive bacteria is attributable exclusively to chromosomal mutations that affect quinolone targets or quinolone permeation to these targets.

Citation: Hooper D. 2006. Mechanisms of Quinolone Resistance, p 821-849. In Fischetti V, Novick R, Ferretti J, Portnoy D, Rood J (ed), Gram-Positive Pathogens, Second Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816513.ch65

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Major Facilitator Superfamily
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Bacterial Proteins
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Bacterial DNA Replication
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Structures of old and newer quinolones.

Citation: Hooper D. 2006. Mechanisms of Quinolone Resistance, p 821-849. In Fischetti V, Novick R, Ferretti J, Portnoy D, Rood J (ed), Gram-Positive Pathogens, Second Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816513.ch65
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Tables

Generic image for table
TABLE 2

Mutations in the GyrB subunit of DNA gyrase and the ParE subunit of topoisomerase IV associated with quinolone resistance

Rows reflect alignments of homologous amino acids.

Amino acids for which genetic data support a role for the mutation in causing resistance. Other mutant amino acids have been associated with resistance in clinical isolates.

Citation: Hooper D. 2006. Mechanisms of Quinolone Resistance, p 821-849. In Fischetti V, Novick R, Ferretti J, Portnoy D, Rood J (ed), Gram-Positive Pathogens, Second Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816513.ch65
Generic image for table
TABLE 1

Mutations in the GyrA subunit of DNA gyrase and the ParC subunit of topoisomerase IV associated with quinolone resistance

Rows reflect alignments of homologous amino acids.

Amino acids for which genetic data support a role for the mutation in causing resistance. Other mutant amino acids have been associated with resistance in clinical isolates.

Citation: Hooper D. 2006. Mechanisms of Quinolone Resistance, p 821-849. In Fischetti V, Novick R, Ferretti J, Portnoy D, Rood J (ed), Gram-Positive Pathogens, Second Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816513.ch65

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