Quinolone resistance from a transferable plasmid

    loading  Checking for direct PDF access through Ovid



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 microgram/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 K 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 microgram/mL and nalidixicacid MIC of 32 microgram/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 microgram/mL and for nalidixic acid of 256 microgram/mL.

Interpretation Transferable resistance to fluoroquinines and nalidixic acid has been found in a clinical isolate of K 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.

Related Topics

    loading  Loading Related Articles