Fluoroquinolone Cellular Targets

Fluoroquinolones function by inhibiting two type 2 topoisomerases: DNA gyrase and topoisomerase IV.[1-3] Type 2 topoisomerases cause staggered single-stranded breaks in both strands of the bacterial chromosome, pass an intact segment of the DNA strand through the break, and reseal the DNA.[1,3-5] Fluoroquinolones bind to the DNA-enzyme complex containing the broken DNA strands forming what is termed the cleavable complex.[3,5-7] DNA repair and replication are inhibited and the resulting release of double-stranded DNA breaks accounts for the bactericidal activity of the fluoroquinol-ones.[1,3]

DNA gyrase is an essential bacterial enzyme formed as a tetramer of two GyrA and two GyrB subunits (A2B2) encoded by gyrA and gyrB, respectively.1-1,3-6-1 DNA gyrase removes superhelical twists ahead of the replication fork and introduces negative supercoils into DNA, which are necessary for replication initiation. Topoiso-merase IV is a tetramer formed of two ParC and two ParE subunits (C2E2), encoded by parC and parE, respectively, that share significant homology with the subunits of DNA gyrase.[1,3-6] Topoisomerase IV's cellular function is the decatenation of sister chromatids during the segregation of replicated chromosomes.[1,3,5]

It was initially believed that the primary target for fluoroquinolones in all gram-negatives, such as Esche-richia coli, was DNA gyrase, whereas the primary target in all gram-positives, such as Staphylococcus aureus, was topoisomerase IV.[1,4] However, it has now been demonstrated that in certain bacterial species, such as S. pneumoniae, the primary bacterial target is dependent on the specific fluoroquinolone structure.[1,4,7]

Getting Started With Dumbbells

Getting Started With Dumbbells

The use of dumbbells gives you a much more comprehensive strengthening effect because the workout engages your stabilizer muscles, in addition to the muscle you may be pin-pointing. Without all of the belts and artificial stabilizers of a machine, you also engage your core muscles, which are your body's natural stabilizers.

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