Fluorescent Labeling of the Antimicrobial Peptide Dendrimer G3KL to Probe Its Entry into Pseudomonas aeruginosa
We recently showed that peptide dendrimer G3KL, with amino acid sequence (KL)8(KKL)4(KKL)2KKL, exerts strong antimicrobial activity against multidrug resistant clinical isolates of the Gram negative bacteria A. Baumanii and P. aeruginosa1,2. G3KL was further shown to have positive impact in burn wound-healing processes and pro-angiogenic effect3. Inspired by imaging studies with fluorescent analogs of the cyclic antimicrobial peptide polymyxin B,4 we have modified G3KL at its C-terminus and obtained fluorescent analogs that retain the antimicrobial activity of G3KL, and used super resolution STED nanoscopy imaging to investigate how these fluorescent G3KL analogs penetrate P. aeruginosa cells.
Figure 1: Structure of the fluorescein labeled peptide dendrimer G3KL and nanoscopy STED imaging of Pseudomonas aeruginosa.
[1] Stach M, Siriwardena TN, Köhler T, van Delden C, Darbre T, Reymond JL, Angew. Chem. Int. Ed. 2014, 53, 12827 –12831
[2] Pires J, Siriwardena TN, Stach M, Tinguely R, Kasraian S, Luzzaro F, Leib SL, Darbre T, Reymond JL, Endimiani A., Antimicrob Agents Chemother. 2015, 59, 7915–7918.
[3] Abdel-Sayed P., Kaeppli A., Siriwardena T., Darbre T., Perron K., Jafari P., Reymond JL., Pioletti DP., Applegate LA., Sci Rep. 2016, 6, 22020
[4] Deris ZZ, Swarbrick JD, Roberts KD, Azad MA, Akter J, Horne AS, Nation RL, Rogers KL, Thompson PE, Velkov T, Li J. Bioconjug Chem. 2014, 25(4), 750-760.