Controlling Persister and Biofilm Cells of Gram-Negative Bacteria with a New 1,3,5-Triazine Derivative
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 incre...
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doaj-b0d0f74dd39f40bc8b9f2dc33c3c4f472020-11-25T02:23:32ZengMDPI AGPharmaceuticals1424-82472015-10-018469671010.3390/ph8040696ph8040696Controlling Persister and Biofilm Cells of Gram-Negative Bacteria with a New 1,3,5-Triazine DerivativeAli Adem Bahar0Zhigang Liu1Meagan Garafalo2Neville Kallenbach3Dacheng Ren4Department of Biomedical and Chemical Engineering, Syracuse University, Syracuse, NY 13244, USADepartment of Chemistry, New York University, New York, NY 10003, USADepartment of Biomedical and Chemical Engineering, Syracuse University, Syracuse, NY 13244, USADepartment of Chemistry, New York University, New York, NY 10003, USADepartment of Biomedical and Chemical Engineering, Syracuse University, Syracuse, NY 13244, USAInfections 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.http://www.mdpi.com/1424-8247/8/4/696antimicrobial peptidebiofilmpersister cellsTN-5Escherichia coliPseudomonas aeruginosa |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Ali Adem Bahar Zhigang Liu Meagan Garafalo Neville Kallenbach Dacheng Ren |
spellingShingle |
Ali Adem Bahar Zhigang Liu Meagan Garafalo Neville Kallenbach Dacheng Ren Controlling Persister and Biofilm Cells of Gram-Negative Bacteria with a New 1,3,5-Triazine Derivative Pharmaceuticals antimicrobial peptide biofilm persister cells TN-5 Escherichia coli Pseudomonas aeruginosa |
author_facet |
Ali Adem Bahar Zhigang Liu Meagan Garafalo Neville Kallenbach Dacheng Ren |
author_sort |
Ali Adem Bahar |
title |
Controlling Persister and Biofilm Cells of Gram-Negative Bacteria with a New 1,3,5-Triazine Derivative |
title_short |
Controlling Persister and Biofilm Cells of Gram-Negative Bacteria with a New 1,3,5-Triazine Derivative |
title_full |
Controlling Persister and Biofilm Cells of Gram-Negative Bacteria with a New 1,3,5-Triazine Derivative |
title_fullStr |
Controlling Persister and Biofilm Cells of Gram-Negative Bacteria with a New 1,3,5-Triazine Derivative |
title_full_unstemmed |
Controlling Persister and Biofilm Cells of Gram-Negative Bacteria with a New 1,3,5-Triazine Derivative |
title_sort |
controlling persister and biofilm cells of gram-negative bacteria with a new 1,3,5-triazine derivative |
publisher |
MDPI AG |
series |
Pharmaceuticals |
issn |
1424-8247 |
publishDate |
2015-10-01 |
description |
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. |
topic |
antimicrobial peptide biofilm persister cells TN-5 Escherichia coli Pseudomonas aeruginosa |
url |
http://www.mdpi.com/1424-8247/8/4/696 |
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