commonly in gyrA and parc.[1,6-10] Mutations are occasionally reported in gyrB and parE, but their contribution to resistance appears to be limited and remains controversial.1-1,6-8,10-1

GyrA Fluoroquinolone Resistance Mutations

The QRDR in GyrA encompasses the region from amino acid 67 to 106.[3] Resistance occurs when amino acids near GyrA's putative active site, Tyr-122, are altered.[3] The specific GyrA amino acids commonly altered in S. pneumoniae fluoroquinolone-resistant isolates are Ser-81 and Glu-85.[1,3,4,8,10] These amino acids are near Tyr-122 in the primary sequence.[4] The mutation of Ser-81 to a tryptophan residue reduces the binding affinity of fluoroquinolones for the gyrase complex.[4] Substitutions of phenylalanine and leucine at position 81 are also prevalent.[1,3,4,8,10] Glu-85 can be mutated to either a lysine or glycine residue.[3,4,8,10] Lysine's positive charge and the steric hindrance resulting from the bulkiness of its side chain may reduce the ability of fluoroquinolones to bind to their targets.[8] The result of all the amino acid substitutions aforementioned for Ser-81 and Glu-85 may be the alteration of the quinolone-binding site structure in the DNA gyrase-DNA complex.[4] A reduced binding affinity for the modified enzyme-DNA complex may be the cause of fluoroquinolone resistance.1-4-1

ParC Fluoroquinolone Resistance Mutations

Similar to GyrA, mutations in the QRDR of ParC alter the quinolone-binding site structure located at the interface of topoisomerase IV and the DNA.[4] The altered structure results in reduced fluoroquinolone binding affinity for the enzyme-DNA complex.[4] The ParC amino acids commonly associated with fluoroquinolone resistance in S.pneumoniae are Ser-79 and Asp-83.[1,3,4,8,10] Ser-79 can be mutated to a phenylalanine or tyrosine resi due.[1,3,4,8,10] Asp-83 can be substituted by alanine, glycine, asparagine, threonine, or tyrosine.[3,8,10] Ser-52 to glycine and Lys-137 to asparagine substitutions have also been reported, although these do not appear to contribute to increased minimum inhibitory concentration (MIC) values.[8] The MIC increases resulting from the development of gyrA and parC mutations are displayed in Table 1.

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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