Natural Products as Platforms To Overcome Antibiotic Resistance.

Natural products have served as powerful therapeutics against pathogenic bacteria since the golden age of antibiotics of the mid-20th century. However, the increasing frequency of antibiotic-resistant infections clearly demonstrates that new antibiotics are critical for modern medicine. Because combinatorial approaches have not yielded effective drugs, we propose that the development of new antibiotics around proven natural scaffolds is the best short-term solution to the rising crisis of antibiotic resistance. We analyze herein synthetic approaches aiming to reengineer natural products into potent antibiotics. Furthermore, we discuss approaches in modulating quorum sensing and biofilm formation as a nonlethal method, as well as narrow-spectrum pathogen-specific antibiotics, which are of interest given new insights into the implications of disrupting the microbiome.

EroS Enzyme from Aliivibrio fischeri Plays Cupid to Choanoflagellates.

Cupid's bow: A collaborative effort by the King and Clardy laboratories has serendipitously identified a bacterial chondroitinase that triggers the choanoflagellate S. rosetta to swarm and sexually reproduce. This unprecedented interaction between a bacterium and a choanoflagellate could give insights into a key evolutionary leap-sexual reproduction.

Diverted Total Synthesis of Promysalin Analogs Demonstrates That an Iron-Binding Motif Is Responsible for Its Narrow-Spectrum Antibacterial Activity.

Promysalin is a species-specific Pseudomonad metabolite with unique bioactivity. To better understand the mode of action of this natural product, we synthesized 16 analogs utilizing diverted total synthesis (DTS). Our analog studies revealed that the bioactivity of promysalin is sensitive to changes within its hydrogen bond network whereby alteration has drastic biological consequences. The DTS library not only yielded three analogs that retained potency but also provided insights that resulted in the identification of a previously unknown ability of promysalin to bind iron. These findings coupled with previous observations hint at a complex multifaceted role of the natural product within the rhizosphere.