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

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.

The ionic liquid [C4mpy][Tf2N] induces bound-like structure in the intrinsically disordered protein FlgM.

The A. aeolicus intrinsically disordered protein FlgM has four well-defined α-helices when bound to σ28, but in water FlgM undergoes a change in tertiary structure. In this work, we investigate the structure of FlgM in aqueous solutions of the ionic liquid [C4mpy][Tf2N]. We find that FlgM is induced to fold by the addition of the ionic liquid, achieving average α-helicity values similar to the bound state. Analysis of secondary structure reveals significant similarity with the bound state, but the tertiary structure is found to be more compact. Interestingly, the ionic liquid is not homogeneously dispersed in the water, but instead aggregates near the protein. Separate simulations of aqueous ionic liquid do not show ion clustering, which suggests that FlgM stabilizes ionic liquid aggregation.