Coatable and Resistance-Proof Ionic Liquid for Pathogen Eradication

Abstract

Antibiotic-resistant bacteria infect close to 3 million people, and kill 35,000, each year in the United States. Ionic liquid (IL)-based antimicrobial agents have the potential to diversify our ever-diminishing antibiotic arsenal. Here, we describe an IL with potent submicromolar antimicrobial activity in vitro against clinically relevant Gram-negative and Gram-positive bacterial pathogens as well as antiinfective activity in a mouse model. The IL kills pathogenic bacteria such as Acinetobacter baumannii, Salmonella enterica, and Escherichia coli by disrupting their outer membrane and does not select for bacterial resistance. We show incorporation of our IL into surface coatings to generate a type of antibiofilm material. The IL-loaded ionogel surfaces demonstrate high-antimicrobial and antifouling activity by killing bacteria in both static and dynamic tests. Our IL-based antibiofilm surfaces are low-cost and easy to manufacture, can be formed on glass, latex, plastic, and metal surfaces, such as catheters and other medical devices where high local concentrations of antimicrobials are needed, and may have applications in other clinical and industrial settings.

Quaternary Ammonium Compounds (QACs) and Ionic Liquids (ILs) as Biocides: From Simple Antiseptics to Tunable Antimicrobials

“…However, ionic polymers with lower levels of ionicity are often considered poly-ILs in publications. In recent years, poly-ILs have been extensively studied as advantageous materials for antibacterial coatings and surfaces [89,[162][163][164][165][166][167][168][169]. Exemplary poly-ILs with tested antibacterial activity are listed in Table 8 and Figure 36.…”

“…(2-Ethylhexyl)ethylenediaminium bis(trifluoromethanesulfonyl)imide-loaded ionogel surface coatings efficiently inhibited the growth of various microorganisms, including those from the ESKAPE list, and prevented the formation of biofilms [163]. Microneedle patches on the basis of salicylic acid-containing API-poly-IL were successfully tested in the treatment of Propionobacterium acnes skin infections [165].…”

“…Thus, the number of publications on the topic has been increasing steadily in recent years. As already mentioned above, ILs are proposed to be used as components of ionogels, films, and membranes that demonstrate considerable antimicrobial and antifouling activities (see, e.g., [89,93,163]). Cellulose nanofibers grafted with ammonium ILs and silver ions demonstrated significant antimicrobial activity against S. aureus MRSA and E. coli [183].…”

Autonomous treatment of bacterial infections in vivo using antimicrobial micro- and nanomachines

“…DiSC 3 -5 is a potentiometric probe that accumulates in the cytoplasmic membrane and aggregates at high concentrations causing fluorescence quenching. 65,66 When the cytoplasmic membrane is depolarized, DiSC 3 -5 migrates to the cytoplasm, leading to increased fluorescence emission intensity (Figure 5a). The micro-and nanomachines with and without AMP had similar ability to depolarize the cytoplasmic membrane of A. baumannii (Figure 5b).…”

“…To assess whether the peptides free in solution and the AMPmodified bioactive micro-and nanomachines were toxic to the animals, the weight of the mice was monitored throughout the experiment. Variations of up to 20% in weight are a widely used proxy of distress, morbidity, and overall toxicity 49,69 . No side effects (e.g., itchiness, redness, swelling) or in vivo toxicity were observed under any of the (which was not certified by peer review) is the author/funder.…”