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Simple Assay Reveals Resistance

 

It has been shown that the induction of fluoroquinolone resistance can be detected by applying Escherichia coli to drug-containing agar and then counting colonies as they accumulate over a week or so. Mutations in genes that inhibit the SOS response blocked accumulation mutants. Karl Drlica of the New Jersey Medical School, Newark, et al. adapted this assay to compare quinolones for the induction of resistance. "Quinolone structure strongly influenced the induction of resistant mutants in parallel with quinolone-mediated killing of wild-type cells," says Drlica. "When we applied the assay to a quinolone-like compound called a 2,4-dione, we found that induction of resistance was restricted relative to a parallel fluoroquinolone." Thus, the assay can be applied to new compounds, and gives the pharmaceutical industry a means, early in drug development, to screen for propensity to generate mutants, he says.

(M. Malik, G. Hoatam, K. Chavda, R. J. Kerns, and K. Drlica. 2010. Novel approach for comparing the abilities of quinolones to restrict the emergence of resistant mutants during quinolone exposure. Antimicrob. Agents Chemother. 54:149-156.)

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