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Updated: Jul 3, 2026

Quadruple-Checkerboard: A Modification of the Three-Dimensional Checkerboard for Studying Drug Combinations
Published on: July 24, 2021
How many modes of action should an antibiotic have?
Heike Brötz-Oesterhelt1, Nina A Brunner
1AiCuris GmbH & Co.KG, Friedrich-Ebert Strasse 475, Building 302, D-42117 Wuppertal, Germany. heike.broetz-oesterhelt@aicuris.com
Abstract:
All antibiotics that have been successfully employed for decades as monotherapeutics in the treatment of bacterial infections rely on mechanisms of bacterial growth inhibition which are by far more complex than inhibition of a single enzyme. Such successful antibiotics have in common that they address several targets in parallel and/or that their targets are encoded by multiple genes. Such multiplicity of targets and of target genes has the advantage that the emergence of spontaneous target-related resistance is a comparatively slow process. Recently registered antibiotics and novel antibiotics in development are discussed in the light of this promising concept of antibacterial polypharmacology.
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