Multi-resistance as a tool for detecting novel beta-lactam antibiotics in the environment

Over the past two decades, antibiotic resistance has become a major clinical and public health problem. The requirement that conventional antibiotics be used at high concentrations and the inability to determine specific antibacterial modes of action against the target cells make conventional methods (e.g., screening large libraries of natural or synthetic molecules) less efficient. This study demonstrates a novel method for the detection of new antibacterial compounds using genetically modified bacteria. Different multi-resistant (MR) bioluminescent strains were developed and exposed to the various β-lactam antibiotics. We show that this MR strain panel is able to determine a specific antibiotic to which a bacterium is not resistant. Furthermore, the MR panel allows the detection of biologically active compounds derived from the environment, and in some cases, these compounds inhibited all bioreporters used, showing that no bacteria were resistant to them. This MR strain panel offers a unique opportunity to improve the biodiscovery of new antibiotics with unknown modes of action, a finding that may facilitate the development of new and effective drugs to which existing bacteria are not resistant.