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In Vitro activity of novel glycopolymer against clinical isolates of multidrug-resistant Staphylococcus aureus.
PLoS One. 2018; 13(1):e0191522.Plos

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.

Authors+Show Affiliations

Synedgen, Inc., Claremont, California, United States of America.Synedgen, Inc., Claremont, California, United States of America.Medical College of Wisconsin, Wisconsin, United States of America.California State University, San Bernardino, United States of America.Synedgen, Inc., Claremont, California, United States of America.Synedgen, Inc., Claremont, California, United States of America.Synedgen, Inc., Claremont, California, United States of America.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

29342216

Citation

Narayanaswamy, Vidya P., et al. "In Vitro Activity of Novel Glycopolymer Against Clinical Isolates of Multidrug-resistant Staphylococcus Aureus." PloS One, vol. 13, no. 1, 2018, pp. e0191522.
Narayanaswamy VP, Giatpaiboon SA, Uhrig J, et al. In Vitro activity of novel glycopolymer against clinical isolates of multidrug-resistant Staphylococcus aureus. PLoS ONE. 2018;13(1):e0191522.
Narayanaswamy, V. P., Giatpaiboon, S. A., Uhrig, J., Orwin, P., Wiesmann, W., Baker, S. M., & Townsend, S. M. (2018). In Vitro activity of novel glycopolymer against clinical isolates of multidrug-resistant Staphylococcus aureus. PloS One, 13(1), e0191522. https://doi.org/10.1371/journal.pone.0191522
Narayanaswamy VP, et al. In Vitro Activity of Novel Glycopolymer Against Clinical Isolates of Multidrug-resistant Staphylococcus Aureus. PLoS ONE. 2018;13(1):e0191522. PubMed PMID: 29342216.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - In Vitro activity of novel glycopolymer against clinical isolates of multidrug-resistant Staphylococcus aureus. AU - Narayanaswamy,Vidya P, AU - Giatpaiboon,Scott A, AU - Uhrig,John, AU - Orwin,Paul, AU - Wiesmann,William, AU - Baker,Shenda M, AU - Townsend,Stacy M, Y1 - 2018/01/17/ PY - 2017/08/30/received PY - 2018/01/05/accepted PY - 2018/1/18/entrez PY - 2018/1/18/pubmed PY - 2018/3/3/medline SP - e0191522 EP - e0191522 JF - PloS one JO - PLoS ONE VL - 13 IS - 1 N2 - 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. SN - 1932-6203 UR - https://www.unboundmedicine.com/medline/citation/29342216/In_Vitro_activity_of_novel_glycopolymer_against_clinical_isolates_of_multidrug_resistant_Staphylococcus_aureus_ L2 - http://dx.plos.org/10.1371/journal.pone.0191522 DB - PRIME DP - Unbound Medicine ER -