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

English version

Autoři: Joshua R. Greene ^aff001; Kahla L. Merrett ^aff001; Alexanndra J. Heyert ^aff001; Lucas F. Simmons ^aff001; Camille M. Migliori ^aff002; Kristen C. Vogt ^aff003; Rebeca S. Castro ^aff003; Paul D. Phillips ^aff001; Joseph L. Baker ^aff003; Gerrick E. Lindberg ^aff001; David T. Fox ^aff005; Rico E. Del Sesto ^aff002; Andrew T. Koppisch ^aff001
Působiště autorů: Department of Chemistry, Northern Arizona University, Flagstaff, AZ, United States of America ^aff001; Department of Chemistry, Dixie State University, St. George, UT, United States of America ^aff002; Department of Chemistry, The College of New Jersey, Ewing, NJ, United States of America ^aff003; Center for Materials Interfaces in Research and Application, Northern Arizona University, Flagstaff, AZ, United States of America ^aff004; Chemistry Division, Los Alamos National Laboratory, Los Alamos, NM, United States of America ^aff005
Vyšlo v časopise: PLoS ONE 14(9)
Kategorie: Research Article
doi: https://doi.org/10.1371/journal.pone.0222211

Souhrn

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.

Klíčová slova:

Biology and life sciences – Microbiology – Biofilms – Bacteriology – Bacterial biofilms – Microbial control – Antimicrobials – Medical microbiology – Microbial pathogens – Bacterial pathogens – Organisms – Bacteria – Staphylococcus – Staphylococcus aureus – Biochemistry – Biochemical simulations – Lipids – Computational biology – Medicine and health sciences – Pharmacology – Drugs – Antibacterials – Pathology and laboratory medicine – Pathogens – Research and analysis methods – Biological cultures – Cell culturing techniques – Biofilm culture – Physical sciences – Chemistry – Chemical compounds – Organic compounds – Alcohols – Ethanol – Organic chemistry

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

Souhrn

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