1.D.71 The Synthetic TP359 Peptide (TP359) Family
TP359 (MYR-KKALK-[K]D-amide, C41H81N9O6) was synthesized with > 95 % purity by Therapeutic Peptides Inc.) is bactericidal against Pseudomonas aeruginosa as determined by reduced bacteria counts, membrane damage and cytoplasmic membrane depolarization, but it was non-toxic to mouse J774 macrophages and human lung A549 epithelial cells (Dosunmu et al. 2016). Electron microscopy analyses showed TP359 bactericidal effects involve structural changes of the bacterium from viable rod-shaped cells to those with cell membrane damage, proceeding into the efflux of cytoplasmic contents and emergence of ghost cells. Gene expression analyses on the effects of TP359 on outer membrane biogenesis genes revealed marked down-regulation, particularly of oprF, which encodes a major structural and outer membrane porin (OprF). In two strains studied, the peptide caused deregulation of outer membrane genes and reduced structural stability. probably leading to cell death (Dosunmu et al. 2016).