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.


RESULTS
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 microg/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 microg/mL and nalidixic-acid MIC of 32 microg/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 microg/mL and for nalidixic acid of 256 microg/mL.


CONCLUSIONS
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.
Martínez-Martínez
L
L
Department of Clinical Microbiology, School of Medicine, University of Seville, Spain.
Pascual
A
A
Jacoby
G A
GA
D000890:Anti-Infective Agents / Q000494:pharmacology*; D002939:Ciprofloxacin / Q000494:pharmacology; D003227:Conjugation, Genetic; D004352:Drug Resistance, Microbial / Q000235:genetics*; D018432:Drug Resistance, Multiple / Q000235:genetics*; D004926:Escherichia coli / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D007711:Klebsiella pneumoniae / Q000187:drug effects* / Q000235:genetics; D009268:Nalidixic Acid / Q000494:pharmacology; D010957:Plasmids / Q000235:genetics*
D000890:Anti-Infective Agents; D009268:Nalidixic Acid; D002939:Ciprofloxacin