Cationic peptide antimicrobials induce selective transcription of micF andosmY in Escherichia coli

Cationic antimicrobial peptides, such as polymyxin and cecropin, activated transcription of osm Y and micF in growing Escherichia coli independently o f each other. The micF response required the presence of a functional rob g ene. It is intriguing that in this and other assays an identical response p rofile was also seen with hyperosmotic salt or sucrose gradient, two of the most commonly used traditional food preservatives. The osm Y and micF tran scription was not induced by hypoosmotic gradient, ionophoric peptides, unc ouplers, or with other classes of membrane perturbing agents. The antibacte rial peptides did not promote transcription of genes that respond to macrom olecular or oxidative damage, fatty acid biosynthesis, heat shock, or deple tion of proton or ion gradients. These and other results show that the anti bacterial cationic peptides induce stasis in the early growth phase, and th e transcriptional efficacy of antibacterial peptides correlates with their minimum inhibitory concentration, and also with their ability to mediate di rect exchange of phospholipids between vesicles. The significance of these results is developed as the hypothesis that the cationic peptide antimicrob ials stress growth of Gramnegative organisms by making contacts between the two phospholipid interfaces in the periplasmic space and prevent the hyper osmotic wrinkling of the cytoplasmic membrane. Broader significance of thes e results, and of the hypothesis that the peptide mediated contacts between the periplasmic phospholipid interfaces are the primary triggers, is discu ssed in relation to antibacterial resistance. (C) 2000 Elsevier Science B.V . All rights reserved.