Kade D. Roberts

TL;DR: In this paper, the authors survey the significant progress over the last decade in understanding polymyxin chemistry, mechanisms of antibacterial activity and resistance, structure-activity relationships and pharmacokinetics/pharmacodynamics.

TL;DR: It is suggested that the inhibition of vital respiratory enzymes in the bacterial inner membrane represents one of the secondary modes of action for polymyxins in response to ubiquinone-1 and NADH.

TL;DR: The results highlight the need to re-assess pharmacopoeial standards for polymyxins B and colistin and to standardize the composition of the different commercial products ofpolymyxin antibiotics.

TL;DR: This report details the structure–activity relationships (SAR) based design, in toto synthesis, and preclinical evaluation of a series of novel polymyxin lipopeptides with better antibacterial activity against poly myxin-resistant Gram-negative bacteria.

TL;DR: The regioselective modification of the polymyxin B core scaffold at the N-terminus with the dansyl fluorophore is reported to generate an active probe that mimics polymy Xin B pharmacologically, which will advance the development of platforms for the discovery of novel polymyXin lipopeptides with efficacy against poly myxin-resistant strains.