Mysterious resistance

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G. A. Jacoby et al. "qnrB, another plasmid-mediated gene for quinolone resistance," Antimicrob Agents Chemother, 50:1178-82, 2006. (Cited in 65 papers)

Eight years after discovering qnrA, the first plasmid-mediated gene for resistance to the broad-spectrum antibiotic quinolone, George Jacoby of the Lahey Clinic found a second resistance gene, qnrB, isolated from strains of the bacteria Klebsiella pneumoniae. After qnrB was cloned and sequenced, a PCR assay revealed it to be as common as qnrA in samples from the United States.

Resistance to quinolones was previously believed to require a chromosomal mutation, says John Blanchard of the Albert Einstein College of Medicine. Now, it is recognized that qnr genes not only move horizontally via plasmid to confer low levels of antibiotic resistance, but they appear to promote "higher levels of quinolone resistance," says David Hooper of Massachusetts General Hospital, a co-author on the paper.

To date, three types of qnr genes have been discovered (qnrS was found in Japan in 2005), as well as 20 strains of qnrB, but a central mystery lingers: The emergence of qnr pre-dates the synthetic creation of quinolones. "So qnr probably has some other function," Jacoby says, "but has been co-opted because it allows them a modicum of resistance."

"We're starting to determine the molecular mechanisms by which these Qnr proteins cause resistance to [quinolone]," Blanchard says. His team has proposed that the protein mimics DNA structure, interacting with quinolone's targeted enzyme, DNA gyrase, so that the antibiotic cannot bind and inhibit it.