Pharmacology

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Science  17 Jun 2011:
Vol. 332, Issue 6036, pp. 1361
DOI: 10.1126/science.332.6036.1361-a

The increasing incidence of drug-resistant strains of pathogenic bacteria and the decreasing frequency of discovery of wholly new antibiotics have induced physicians to consider administering more than one drug at a time. How to design these regimens is explored in two studies.

Bollenbach and Kishony have studied the effects of a trio of antibiotics, two of which target the small and large ribosomal subunits, with the third being an antifolate. Applying these two at a time in varying concentrations to an Escherichia coli library revealed that the transcriptional response is primarily governed by the overall effect of restraining growth and secondarily predicted by either the average (if the two drugs were agonistic) or the lower bound (for the antagonistic pairings).

Ejim et al. have screened a chemical database of nonantibiotic drugs for compounds that enhance the efficacy of minocycline against E. coli, Pseudomonas aeruginosa, Staphylococcus aureus, and Salmonella enterica. One of the candidates was loperamide (Imodium); the mechanism of synergy probably involves changes in membrane permeability on the basis of in vivo tests in a mouse model of infectious colitis.

Mol. Cell 42, 413 (2011); Nat. Chem. Biol. 7, 348 (2011).

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