Scope and efficacy of the broad-spectrum topical antiseptic choline geranate

Greene, Joshua R.; Merrett, Kahla L.; Heyert, Alexanndra J.; Simmons, Lucas F.; Migliori, Camille M.; Vogt, Kristen C.; Castro, Rebeca S.; Phillips, Paul D.; Baker, Joseph L.; Lindberg, Gerrick E.; Fox, David T.; Del Sesto, Rico E.; Koppisch, Andrew T.

doi:10.1371/journal.pone.0222211

Title: Scope and efficacy of the broad-spectrum topical antiseptic choline geranate

Journal Article · 17 September 2019 · PLoS ONE

DOI: https://doi.org/10.1371/journal.pone.0222211 · OSTI ID:1597369

Greene, Joshua R. ^[1]; Merrett, Kahla L. ^[1]; Heyert, Alexanndra J. ^[1]; Simmons, Lucas F. ^[1]; Migliori, Camille M. ^[2]; Vogt, Kristen C. ^[3]; Castro, Rebeca S. ^[3]; Phillips, Paul D. ^[1]; Baker, Joseph L. ^[3];

^[1];

^[4]; Del Sesto, Rico E. ^[2];

^[1]

Northern Arizona Univ., Flagstaff, AZ (United States)
Dixie State Univ., St. George, UT (United States)
The College of New Jersey, Ewing, NJ (United States)
Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

Choline geranate (also described as Choline And GEranic acid, or CAGE) has been developed as a novel biocompatible antiseptic material capable of penetrating skin and aiding the transdermal delivery of co-administered antibiotics. The antibacterial properties of CAGE were analyzed against 24 and 72 hour old biofilms of 11 clinically isolated ESKAPE pathogens (defined as Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumanii, Pseudomonas aeruginosa, and Enterobacter sp, respectively), including multidrug resistant (MDR) isolates. CAGE was observed to eradicate in vitro biofilms at concentrations as low as 3.56 mM (0.156% v:v) in as little as 2 hours, which represents both an improved potency and rate of biofilm eradication relative to that reported for most common standard-of-care topical antiseptics in current use. In vitro time-kill studies on 24 hour old Staphylococcus aureus biofilms indicate that CAGE exerts its antibacterial effect upon contact and a 0.1% v:v solution reduced biofilm viability by over three orders of magnitude (a 3log10 reduction) in 15 minutes. Furthermore, disruption of the protective layer of exopolymeric substances in mature biofilms of Staphylococcus aureus by CAGE (0.1% v:v) was observed in 120 minutes. Insight into the mechanism of action of CAGE was provided with molecular modeling studies alongside in vitro antibiofilm assays. The geranate ion and geranic acid components of CAGE are predicted to act in concert to integrate into bacterial membranes, affect membrane thinning and perturb membrane homeostasis. Taken together, our results show that CAGE demonstrates all properties required of an effective topical antiseptic and the data also provides insight into how its observed antibiofilm properties may manifest.

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Research Organization:: Los Alamos National Laboratory (LANL), Los Alamos, NM (United States)

Sponsoring Organization:: USDOE

Grant/Contract Number:: 89233218CNA000001; OAC-1828163; OAC-1826915

OSTI ID:: 1597369

Report Number(s):: LA-UR-19-31572

Journal Information:: PLoS ONE, Vol. 14, Issue 9; ISSN 1932-6203

Publisher:: Public Library of ScienceCopyright Statement

Country of Publication:: United States

Language:: English

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Cited by: 14 works

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Diverted Total Synthesis of Carolacton-Inspired Analogs Yields Three Distinct Phenotypes in Streptococcus mutans Biofilms Solinski, Amy E.; Koval, Alexander B.; Brzozowski, Richard S. Journal of the American Chemical Society, Vol. 139, Issue 21 https://doi.org/10.1021/jacs.7b03879	journal	May 2017
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In vitro antimicrobial studies of silver carbene complexes: activity of free and nanoparticle carbene formulations against clinical isolates of pathogenic bacteria Leid, J. G.; Ditto, A. J.; Knapp, A. Journal of Antimicrobial Chemotherapy, Vol. 67, Issue 1 https://doi.org/10.1093/jac/dkr408	journal	October 2011
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Development of a Native Escherichia coli Induction System for Ionic Liquid Tolerance Frederix, Marijke; Hütter, Kimmo; Leu, Jessica PLoS ONE, Vol. 9, Issue 7 https://doi.org/10.1371/journal.pone.0101115	journal	July 2014
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Membrane Thinning and Thickening Induced by Membrane-Active Amphipathic Peptides Grage, Stephan L.; Afonin, Sergii; Kara, Sezgin Karlsruhe https://doi.org/10.5445/ir/1000057825	text	January 2016

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Related Subjects

59 BASIC BIOLOGICAL SCIENCES
Biological Science
choline geranate
antiseptic
antibiofilm
ionic liquids
deep eutectic solvent
ESKAPE pathogens

Title: Scope and efficacy of the broad-spectrum topical antiseptic choline geranate

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References (76)

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