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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Main Authors:	Bahar, Ali Adem, Liu, Zhigang, Garafalo, Meagan, Kallenbach, Neville, Ren, Dacheng
Format:	Online
Language:	English
Published:	MDPI 2015
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4695806/

id	pubmed-4695806
recordtype	oai_dc
spelling	pubmed-46958062016-01-19 Controlling Persister and Biofilm Cells of Gram-Negative Bacteria with a New 1,3,5-Triazine Derivative Bahar, Ali Adem Liu, Zhigang Garafalo, Meagan Kallenbach, Neville Ren, Dacheng Article 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. MDPI 2015-10-10 /pmc/articles/PMC4695806/ /pubmed/26473884 http://dx.doi.org/10.3390/ph8040696 Text en © 2015 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/4.0/).
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Bahar, Ali Adem Liu, Zhigang Garafalo, Meagan Kallenbach, Neville Ren, Dacheng
spellingShingle	Bahar, Ali Adem Liu, Zhigang Garafalo, Meagan Kallenbach, Neville Ren, Dacheng Controlling Persister and Biofilm Cells of Gram-Negative Bacteria with a New 1,3,5-Triazine Derivative
author_facet	Bahar, Ali Adem Liu, Zhigang Garafalo, Meagan Kallenbach, Neville Ren, Dacheng
author_sort	Bahar, Ali Adem
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
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.
publisher	MDPI
publishDate	2015
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4695806/
_version_	1613518172575498240

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

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