Instructive Advances in Chemical Microbiology Inspired by Nature's Diverse Inventory of Molecules

Natural product antibiotics have played an essential role in the treatment of bacterial infection in addition to serving as useful tools to explore the intricate biology of bacteria. Our current arsenal of antibiotics operate through the inhibition of well-defined bacterial targets critical for replication and growth. Pathogenic bacteria effectively utilize a diversity of mechanisms that lead to acquired resistance and/or innate tolerance toward antibiotic therapies, which can result in devastating consequences to human life. Several research groups have established innovative programs that work at the chemistry-biology interface to develop new molecules that aim to define and address concerns related to antibiotic resistance and tolerance. In this Review, we present recent progress by select research groups that highlight a diversity of integrated chemical biology and medicinal chemistry approaches aimed at the development and utilization of chemical tools that have led to promising new microbiological insights that may lead to significant clinical advances regarding the treatment of pathogenic bacteria.