Mechanisms of resistance to fluoroquinolones: state-of-the-art 1992-1994.
This paper gives an update on the mechanisms of bacterial resistance to fluoroquinolones. The laboratory techniques currently used to determine the mechanism(s) of resistance are outlined, including the use of restriction fragment length polymorphism and single-stranded conformational polymorphism analysis of mutations in gyrA. Alterations in gyrA have continued to be the most reported cause of resistance, with high level resistance due to 2 or more mutations in this gene. Recently, mutations in gyrA of Mycobacterium tuberculosis and Campylobacter jejuni have been described. Complementation studies with plasmid encoded cloned gyrB from Escherichia coli suggest that high fluoroquinolone resistance (minimum inhibitory concentration = 32 mg/L) in Salmonella typhimurium can be due to mutation in both gyrA and gyrB. Decreased fluoroquinolone accumulation into E. coli has been shown to be due to mutations in a number of genes at different loci. Current interest has focused upon the marRAB and soxRS loci, with mutations in genes of either loci giving rise to decreased susceptibility to several unrelated drugs, including fluoroquinolones, tetracycline, chloramphenicol and some beta-lactams, and decreased expression of OmpF. The genetic characterisation of fluoroquinolone efflux from Staphylococcus aureus has shown that efflux occurs in both fluoroquinolone-susceptible and -resistant bacteria. The most likely cause of resistance is overexpression of NorA, giving rise to increased efflux. Recently, 2 efflux systems in Pseudomonas aeruginosa have been proposed, MexA-MexB-OprK and MexC-MexD-OprM, conferring decreased susceptibility to fluoroquinolones, tetracycline, chloramphenicol and some beta-lactams.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Infection, University of Birmingham, England.
L J
LJ
Piddock
D000818:Animals; D000890:Anti-Infective Agents / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics; D004250:DNA Topoisomerases, Type II / Q000378:metabolism; D004352:Drug Resistance, Microbial; D024841:Fluoroquinolones; D006801:Humans
D000890:Anti-Infective Agents; D024841:Fluoroquinolones; D004250:DNA Topoisomerases, Type II