Mechanisms of resistance to quinolones.
Mechanisms of resistance to the quinolones have been described for several bacterial species, but mainly for Escherichia coli and Staphylococcus aureus. Two principal mechanisms have been described: 1) alteration of the DNA gyrase, which is the target site of the quinolones; and 2) diminished accumulation in the cell as a result of either decreased uptake or increased efflux. Alteration of DNA gyrase is usually the result of a mutation in the gyrA, or more rarely, the gyrB gene. All substitutions in subunit A of the gyrase are located in the 67 to 106 amino-acid domain and are clustered around Ser-83 in E. coli and Ser-84 in S. aureus. A decrease in uptake has been described for Gram-negative bacteria such as Enterobacteriaceae and Pseudomonas aeruginosa. It has almost always been correlated with a modified electrophoretic profile of outer membrane proteins of the quinolone-resistant mutants. In E. coli, a decrease in OmpF seemed to be linked to the activation of the micF operon in most of the mutants described. These mutants were cross-resistant to unrelated antibiotics, such as trimethoprim, chloramphenicol, tetracycline, and some beta-lactams. In all these mutants the normal or enhanced efflux of quinolones increased the level of resistance. Enhanced efflux has been described as the second mechanism of resistance in S. aureus. Acquired resistance to the quinolones was thought, until recently, to result from chromosomal mutation. Plasmid-mediated resistance associated with an enhanced efflux has been described in S. aureus, but this needs to be confirmed. When a high level of resistance is observed, 2 or 3 mechanisms may be involved.(ABSTRACT TRUNCATED AT 250 WORDS)
Cambau
E
E
Laboratoire de Bacteriologie-Virologie, CHU Pitié-Salpêtrière, Université Paris VI, France.
Gutmann
L
L
D042462:4-Quinolones; D000890:Anti-Infective Agents / Q000494:pharmacology*; D002463:Cell Membrane Permeability / Q000187:drug effects; D004250:DNA Topoisomerases, Type II / Q000187:drug effects*; D004352:Drug Resistance, Microbial / Q000235:genetics; D006090:Gram-Negative Bacteria / Q000187:drug effects; D006094:Gram-Positive Bacteria / Q000187:drug effects
D042462:4-Quinolones; D000890:Anti-Infective Agents; D004250:DNA Topoisomerases, Type II