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

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

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Article numbere0222211
JournalPLoS ONE
Volume14
Issue number9
DOIs
StatePublished - Jan 1 2019

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antiseptics
Local Anti-Infective Agents
Biofilms
choline
Choline
biofilm
Staphylococcus aureus
Membranes
Staphylococcal Pneumonia
Enterococcus faecium
Enterobacter
Acinetobacter
Time and motion study
Molecular modeling
antibacterial properties
Klebsiella pneumoniae
acids
Biocompatible Materials
Pathogens
Standard of Care

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Greene, J. R., Merrett, K. L., Heyert, A. J., Simmons, L. F., Migliori, C. M., Vogt, K. C., ... Koppisch, A. T. (2019). Scope and efficacy of the broad-spectrum topical antiseptic choline geranate. PLoS ONE, 14(9), [e0222211]. https://doi.org/10.1371/journal.pone.0222211

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.

In: PLoS ONE, Vol. 14, No. 9, e0222211, 01.01.2019.

Research output: Contribution to journalArticle

Greene, JR, Merrett, KL, Heyert, AJ, Simmons, LF, Migliori, CM, Vogt, KC, Castro, RS, Phillips, PD, Baker, JL, Lindberg, GE, Fox, DT, Del Sesto, RE & Koppisch, AT 2019, 'Scope and efficacy of the broad-spectrum topical antiseptic choline geranate', PLoS ONE, vol. 14, no. 9, e0222211. https://doi.org/10.1371/journal.pone.0222211
Greene JR, Merrett KL, Heyert AJ, Simmons LF, Migliori CM, Vogt KC et al. Scope and efficacy of the broad-spectrum topical antiseptic choline geranate. PLoS ONE. 2019 Jan 1;14(9). e0222211. https://doi.org/10.1371/journal.pone.0222211
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. / Scope and efficacy of the broad-spectrum topical antiseptic choline geranate. In: PLoS ONE. 2019 ; Vol. 14, No. 9.
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