» Articles » PMID: 29342216

In Vitro Activity of Novel Glycopolymer Against Clinical Isolates of Multidrug-resistant Staphylococcus Aureus

Overview
Journal PLoS One
Date 2018 Jan 18
PMID 29342216
Citations 5
Authors
Affiliations
Soon will be listed here.
Abstract

The incidence of multidrug-resistant (MDR) organisms, including methicillin-resistant Staphylococcus aureus (MRSA), is a serious threat to public health. Progress in developing new therapeutics is being outpaced by antibiotic resistance development, and alternative agents that rapidly permeabilize bacteria hold tremendous potential for treating MDR infections. A new class of glycopolymers includes polycationic poly-N (acetyl, arginyl) glucosamine (PAAG) is under development as an alternative to traditional antibiotic strategies to treat MRSA infections. This study demonstrates the antibacterial activity of PAAG against clinical isolates of methicillin and mupirocin-resistant Staphylococcus aureus. Multidrug-resistant S. aureus was rapidly killed by PAAG, which completely eradicated 88% (15/17) of all tested strains (6-log reduction in CFU) in ≤ 12-hours at doses that are non-toxic to mammalian cells. PAAG also sensitized all the clinical MRSA strains (17/17) to oxacillin as demonstrated by the observed reduction in the oxacillin MIC to below the antibiotic resistance breakpoint. The effect of PAAG and standard antibiotics including vancomycin, oxacillin, mupirocin and bacitracin on MRSA permeability was studied by measuring propidium iodide (PI) uptake by bacterial cells. Antimicrobial resistance studies showed that S. aureus developed resistance to PAAG at a rate slower than to mupirocin but similar to bacitracin. PAAG was observed to resensitize drug-resistant S. aureus strains sampled from passage 13 and 20 of the multi-passage resistance study, reducing MICs of mupirocin and bacitracin below their clinical sensitivity breakpoints. This class of bacterial permeabilizing glycopolymers may provide a new tool in the battle against multidrug-resistant bacteria.

Citing Articles

Soluble chitosan derivative treats wound infections and promotes wound healing in a novel MRSA-infected porcine partial-thickness burn wound model.

Egro F, Repko A, Narayanaswamy V, Ejaz A, Kim D, Schusterman M PLoS One. 2022; 17(10):e0274455.

PMID: 36240206 PMC: 9565743. DOI: 10.1371/journal.pone.0274455.


Polycationic Glycopolymer Demonstrates Activity Against Persisters and Biofilms of Non-tuberculosis Cystic Fibrosis Clinical Isolates .

Narayanaswamy V, Townsend S, Loughran A, Wiesmann W, Baker S Front Microbiol. 2022; 13:821820.

PMID: 35265060 PMC: 8900536. DOI: 10.3389/fmicb.2022.821820.


Treatment of Pulmonary Disease of Cystic Fibrosis: A Comprehensive Review.

Giron Moreno R, Garcia-Clemente M, Diab-Caceres L, Martinez-Vergara A, Martinez-Garcia M, Gomez-Punter R Antibiotics (Basel). 2021; 10(5).

PMID: 33922413 PMC: 8144952. DOI: 10.3390/antibiotics10050486.


Improving the antimicrobial efficacy against resistant Staphylococcus aureus by a combined use of conjugated oligoelectrolytes.

Bazan E, Ruan L, Zhou C PLoS One. 2019; 14(11):e0224816.

PMID: 31730663 PMC: 6857938. DOI: 10.1371/journal.pone.0224816.


Novel Glycopolymer Eradicates Antibiotic- and CCCP-Induced Persister Cells in .

Narayanaswamy V, Keagy L, Duris K, Wiesmann W, Loughran A, Townsend S Front Microbiol. 2018; 9:1724.

PMID: 30123191 PMC: 6085434. DOI: 10.3389/fmicb.2018.01724.

References
1.
Hurdle J, ONeill A, Ingham E, Fishwick C, Chopra I . Analysis of mupirocin resistance and fitness in Staphylococcus aureus by molecular genetic and structural modeling techniques. Antimicrob Agents Chemother. 2004; 48(11):4366-76. PMC: 525403. DOI: 10.1128/AAC.48.11.4366-4376.2004. View

2.
Farrell D, Robbins M, Rhys-Williams W, Love W . Investigation of the potential for mutational resistance to XF-73, retapamulin, mupirocin, fusidic acid, daptomycin, and vancomycin in methicillin-resistant Staphylococcus aureus isolates during a 55-passage study. Antimicrob Agents Chemother. 2010; 55(3):1177-81. PMC: 3067113. DOI: 10.1128/AAC.01285-10. View

3.
Dasenbrook E, Checkley W, Merlo C, Konstan M, Lechtzin N, Boyle M . Association between respiratory tract methicillin-resistant Staphylococcus aureus and survival in cystic fibrosis. JAMA. 2010; 303(23):2386-92. DOI: 10.1001/jama.2010.791. View

4.
Stein C, Makarewicz O, Bohnert J, Pfeifer Y, Kesselmeier M, Hagel S . Three Dimensional Checkerboard Synergy Analysis of Colistin, Meropenem, Tigecycline against Multidrug-Resistant Clinical Klebsiella pneumonia Isolates. PLoS One. 2015; 10(6):e0126479. PMC: 4465894. DOI: 10.1371/journal.pone.0126479. View

5.
Kollef M . Limitations of vancomycin in the management of resistant staphylococcal infections. Clin Infect Dis. 2007; 45 Suppl 3:S191-5. DOI: 10.1086/519470. View