Quinolone resistance from a transferable plasmid

Background Bacteria can mutate to acquire quinolone resistance by target alterations or diminished drug accumulation. Plasmid-mediated resistance to quinolones in clinical isolates has been claimed but not confirmed. We investigated whether a multiresistance plasmid could transfer resistance to quinolones between bacteria. Methods We transferred resistance between strains by conjugation. The resistance plasmid was visualised in different hosts by agarose-gel electrophoresis. We determined the frequency of spontaneous mutations to ciprofloxacin or nalidixic-acid resistance in Escherichia coli strains, with or without the quinolone resistance plasmid. Findings A multiresistance plasmid (pMG252) from a clinical isolate of Klebsiella pneumoniae was found to increase quinolone resistance to minimum inhibitory concentrations (MICs) as high as 32 mu g/mL for ciprofloxacin when transferred to strains of K pneumoniae deficient in outer-membrane porins. Much lower resistance was seen when pMG252 was introduced into It pneumoniae or E coli strains with normal porins. The plasmid had a wide host range and expressed quinolone resistance in other enterobacteriaceae and in Pseudomonas aeruginosa. From a plasmid-containing E coli strain with ciprofloxacin MIC of 0.25 mu g/mL and nalidixic-acid MIC of 32 mu g/mL, quinolone-resistant mutants could be obtained at more than 100 times the frequency of a plasmid-free strain, reaching MICs for ciprofloxacin of 4 mu g/mL and for nalidixic acid of 256 mu g/mL. Interpretation Transferable resistance to fluoroquinines and nalidixic acid has been found in a clinical isolate of It pneumoniae on a broad host range plasmid. Although resistance was low in wild-type strains, higher levels of quinolone resistance arose readily by mutation. Such a plasmid can speed the development and spread of resistance to these valuable antimicrobial agents.