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Pharmaceuticals 2015, 8(4), 696-710; doi:10.3390/ph8040696

Controlling Persister and Biofilm Cells of Gram-Negative Bacteria with a New 1,3,5-Triazine Derivative

1
Department of Biomedical and Chemical Engineering, Syracuse University, Syracuse, NY 13244, USA
2
Syracuse Biomaterials Institute, Syracuse University, Syracuse, NY 13244, USA
3
Department of Chemistry, New York University, New York, NY 10003, USA
4
Department of Civil and Environmental Engineering, Syracuse University, Syracuse, NY 13244, USA
5
Department of Biology, Syracuse University, Syracuse, NY 13244, USA
These authors contributed equally to this work.
*
Authors to whom correspondence should be addressed.
Academic Editor: Jean Jacques Vanden Eynde
Received: 28 July 2015 / Accepted: 28 September 2015 / Published: 10 October 2015
(This article belongs to the Special Issue Microbial Biofilms)
View Full-Text   |   Download PDF [1675 KB, uploaded 10 October 2015]   |  

Abstract

Infections caused by multidrug-resistant bacteria have been on the rise. This important issue presents a great challenge to the healthcare system and creates an urgent need for alternative therapeutic agents. As a potential solution to this problem, antimicrobial peptides (AMPs) have attracted increasing attention due to their broad spectrum of targeted microbes. However, most AMPs are expensive to synthesize, have relatively high cytotoxicity to mammalian cells, and are susceptible to proteolytic degradation. In order to overcome these limitations, novel synthetic AMPs are desired. Using 1,3,5-triazine (TN) as a template, several combinatorial libraries with varying cationic charge and lipophilicity were designed and screened by the Kallenbach lab. From this screening, TN-5 was identified as a potent lead. In the present study, this compound was tested for its antimicrobial activities on Escherichia coli and Pseudomonas aeruginosa. In addition to regular planktonic cells, the effects on biofilms and persister cells (metabolically inactive and antibiotic tolerant subpopulation) were also investigated. TN-5 was found to have a minimum inhibitory concentration (MIC) of 12.8 μM for both species and kill regular planktonic cells of both species dose dependently. TN-5 is also effective against persister cells of both E. coli and P. aeruginosa. The killing of biofilm cells of the mucoid P. aeruginosa PDO300 was enhanced by alginate lyase. View Full-Text
Keywords: antimicrobial peptide; biofilm; persister cells; TN-5; Escherichia coli; Pseudomonas aeruginosa antimicrobial peptide; biofilm; persister cells; TN-5; Escherichia coli; Pseudomonas aeruginosa
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Bahar, A.A.; Liu, Z.; Garafalo, M.; Kallenbach, N.; Ren, D. Controlling Persister and Biofilm Cells of Gram-Negative Bacteria with a New 1,3,5-Triazine Derivative. Pharmaceuticals 2015, 8, 696-710.

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