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Novel Glycopolymer Eradicates Antibiotic- and CCCP-Induced Persister Cells in Pseudomonas aeruginosa

Authors :
Vidya P. Narayanaswamy
Laura L. Keagy
Kathryn Duris
William Wiesmann
Allister J. Loughran
Stacy M. Townsend
Shenda Baker
Source :
Frontiers in Microbiology, Vol 9 (2018)
Publication Year :
2018
Publisher :
Frontiers Media S.A., 2018.

Abstract

Antibiotic treatments often fail to completely eradicate a bacterial infection, leaving behind an antibiotic-tolerant subpopulation of intact bacterial cells called persisters. Persisters are considered a major cause for treatment failure and are thought to greatly contribute to the recalcitrance of chronic infections. Pseudomonas aeruginosa infections are commonly associated with elevated levels of drug-tolerant persister cells, posing a serious threat to human health. This study represents the first time a novel large molecule polycationic glycopolymer, poly (acetyl, arginyl) glucosamine (PAAG), has been evaluated against antibiotic and carbonyl cyanide m-chlorophenylhydrazone induced P. aeruginosa persisters. PAAG eliminated eliminated persisters at concentrations that show no significant cytotoxicity on human lung epithelial cells. PAAG demonstrated rapid bactericidal activity against both forms of induced P. aeruginosa persister cells resulting in complete eradication of the in vitro persister cells within 24 h of treatment. PAAG demonstrated greater efficacy against persisters in vitro than antibiotics currently being used to treat persistent chronic infections such as tobramycin, colistin, azithromycin, aztreonam, and clarithromycin. PAAG caused rapid permeabilization of the cell membrane and caused significant membrane depolarization in persister cells. PAAG efficacy against these bacterial subpopulations suggests it may have substantial therapeutic potential for eliminating recurrent P. aeruginosa infections.

Details

Language :
English
ISSN :
1664302X
Volume :
9
Database :
Directory of Open Access Journals
Journal :
Frontiers in Microbiology
Publication Type :
Academic Journal
Accession number :
edsdoj.12f0b587d45748b596ff2666451c7318
Document Type :
article
Full Text :
https://doi.org/10.3389/fmicb.2018.01724