Antibiotic interceptors: Creating safe spaces for bacteria

Antibiotics have underpinned numerous advances including surgery, organ transplantation, and cancer chemotherapy. Therefore, the emergence of bacterial pathogens that are resistant to therapeutic antibiotics poses enormous challenges to modern medicine [1]. One of the key mechanisms by which bacteria resist antibiotics is the production of enzymes that inactivate antibacterial molecules via hydrolysis or chemical modification [1]. However, there is growing evidence that bacteria can also survive exposure to antibiotics by releasing molecules into the extracellular space that sequester the drug and prevent it from reaching its target. Some of these ‘antibiotic interceptors’ function as decoys by mimicking target molecules, whilst others share no obvious similarity to the target at all (Fig 1). Many interceptors also function as structural components of biofilms, thereby contributing to the antibiotic tolerance of these bacterial communities. This article summarises our current understanding of antibiotic interceptors, explores the selection pressures for the emergence of these systems, and identifies future research avenues to characterise and overcome antimicrobial interception strategies.