High-Throughput Discovery of Synthetic Siderophores for Trojan Horse Antibiotics.

ABSTRACT: To cause infection, bacterial pathogens must overcome host immune factors and barriers to nutrient acquisition. Reproducing these aspects of host physiology in vitro has shown great promise for antibacterial drug discovery. When used as a bacterial growth medium, human serum replicates several aspects of the host environment, including innate immunity and iron limitation. We previously reported that a high-throughput chemical screen using serum as the growth medium enabled the discovery of novel growth inhibitors overlooked by conventional screens. Here, we report that a subset of compounds from this high-throughput serum screen display an unexpected growth enhancing phenotype and are enriched for synthetic siderophores. We selected 35 compounds of diverse chemical structure and quantified

SUBMITTER: Weber BS 

PROVIDER: S-EPMC11556397 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature