Mechanism of the Antibacterial Activity and Resistance of Polymyxins

Abstract

Discovered in the 1940s, polymyxins are antimicrobial peptides produced by the Gram-positive soil bacterium, Paenibacillus polymyxa, which biosynthesizes polymyxins using non-ribosomal peptide synthetase enzymes [1–3]. Polymyxin B and E (polymyxin E was originally named colistin but was determined to have an identical structure) were used clinically in the late 1950s against Gram-negative bacterial infections [4, 5]. However, nephrotoxic and neurotoxic effects of polymyxin treatment became evident, causing a decline in the use of the polymyxins in the 1970s [6]. Soon, newer antibiotics, such as the aminoglycosides, replaced polymyxins in the clinic. However, since the early 2000s the emergen..