caa a22 4500 60549889X CHVBK 20210128100548.0 cr unu---uuuuu 210128e20151001xx s 000 0 eng 10.1007/s00253-015-6645-7 doi (NATIONALLICENCE)springer-10.1007/s00253-015-6645-7 Synthetic dendrimeric peptide active against biofilm and persister cells of Pseudomonas aeruginosa [Elektronische Daten] [Ali Bahar, Zhigang Liu, Filbert Totsingan, Carlos Buitrago, Neville Kallenbach, Dacheng Ren] Antimicrobial dendrimeric peptides (AMDP) are a relatively new class of agents displaying repetitive functional groups on a branched core. Previously, we have investigated the length requirement for antimicrobial activity of peptides consisting of repeated arginine (R) and tryptophan (W) side chains and found that even short linear RW repeats are active, providing a starting point for a de novo design of multivalent structures. In this study, we synthesized and tested a new synthetic dendrimer, 2D-24, for its antimicrobial activity against Pseudomonas aeruginosa, including the wild-type PAO1 and its mucoid mutant PDO300. This synthetic AMDP was found to kill planktonic cells of both PAO1 and PDO300 in a dose-dependent manner, with nearly complete killing of both strains observed when treated with 50μM of this agent. In addition to planktonic cells, 2D-24 was also found to kill biofilm cells of both strains in a dose-dependent manner. For example, treatment with 30μM 2D-24 led to 94.4 ± 1.4 and 93.9 ± 4.2% killing of PAO1 and PDO300 biofilm cells, respectively. Furthermore, 2D-24 was effective in killing multidrug-tolerant persister cells of PAO1 and PDO300. While higher concentrations of 2D-24 were required to kill persister cells, combinations of 2D-24 with ciprofloxacin, tobramycin, or carbenicillin showed synergistic effects on killing persister cells of both strains. Based on hemolysis assays using sheep erythrocytes and a coculture model of PAO1 and human epithelial cells, 2D-24 was found to kill P. aeruginosa cells at concentrations that are not toxic to mammalian cells. Springer-Verlag Berlin Heidelberg, 2015 Pseudomonas aeruginosa nationallicence Antimicrobial peptide nationallicence Biofilm nationallicence Persister cells nationallicence Killing nationallicence Bahar Ali Department of Biomedical and Chemical Engineering, Syracuse University, Syracuse, NY, USA aut Liu Zhigang Department of Chemistry, New York University, New York, NY, USA aut Totsingan Filbert Department of Chemistry, New York University, New York, NY, USA aut Buitrago Carlos Department of Chemistry, New York University, New York, NY, USA aut Kallenbach Neville Department of Chemistry, New York University, New York, NY, USA aut Ren Dacheng Department of Biomedical and Chemical Engineering, Syracuse University, Syracuse, NY, USA aut Applied Microbiology and Biotechnology Springer Berlin Heidelberg 99/19(2015-10-01), 8125-8135 0175-7598 99:19<8125 2015 99 253 https://doi.org/10.1007/s00253-015-6645-7 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s00253-015-6645-7 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Bahar Ali Department of Biomedical and Chemical Engineering, Syracuse University, Syracuse, NY, USA aut NATIONALLICENCE 700 1- Liu Zhigang Department of Chemistry, New York University, New York, NY, USA aut NATIONALLICENCE 700 1- Totsingan Filbert Department of Chemistry, New York University, New York, NY, USA aut NATIONALLICENCE 700 1- Buitrago Carlos Department of Chemistry, New York University, New York, NY, USA aut NATIONALLICENCE 700 1- Kallenbach Neville Department of Chemistry, New York University, New York, NY, USA aut NATIONALLICENCE 700 1- Ren Dacheng Department of Biomedical and Chemical Engineering, Syracuse University, Syracuse, NY, USA aut NATIONALLICENCE 773 0- Applied Microbiology and Biotechnology Springer Berlin Heidelberg 99/19(2015-10-01), 8125-8135 0175-7598 99:19<8125 2015 99 253