Super Surfaces: Pulverizing Polymers Out-Muscle Pesky Pathogens

Materials also possess varying innate degrees of bacteria-friendliness. A recent study conducted by the Centre for Applied Microbiology & Research (Salisbury, U.K.) revealed that metals commonly used to manufacture food-contact surfaces harbor bacteria for much longer than an average work shift, some almost indefinitely. The most common food-processing surface, stainless steel, retains live bacteria for 34 days and copper, which is known to possess anti-microbial properties, retains viable pathogens for up to 14 hours. [See News & Notes, Food Quality, February/March, p. 18]

The activity of monomer or small-molecule AACs as therapeutics, while not directly applicable to food processing, illustrates the potential of the related polymers in the food marketplace. AACs suitable for human or veterinary drugs have demonstrated characteristics that positively distinguish them from host defense peptides or –for that matter – any other synthetic antibiotic or compound.

In studies using rodent models of bacterial infection, AACs have shown a level of safety and efficacy orders of magnitude more favorable than for host defense peptides, not to mention many marketed antibiotics. Some relevant characteristics of these molecules, which translate to the polymeric materials, include:

• Systemic activity in animals against multiple bacterial diseases;
• Selectivity for bacteria vs. human cells of 100 to greater than 10,000, compared with 10- to 20-fold for host defense proteins;
• Well tolerated in animals at blood levels more than 300 times higher than bactericidal concentrations;
• Excellent drug-like properties – pharmacokinetics, half-life, serum binding, and tolerability profiles are characteristic of safe, effective drugs;< /li>
• Ease of manufacture – chemical synthetic schemes comparable to those for manufacturing drugs or polymeric materials.

AACs work by exploiting the unique chemical composition of bacterial cell membranes. Bacteria contain more negatively charged chemical groups on the outer surface of their membranes than do mammalian cells. Bacterial membranes also lack cholesterol, an essential component of all mammalian membranes. AACs home in on membranes that lack cholesterol and which contain large numbers of negatively-charged phospholipids – thus, they are specific and selective for bacterial cell membranes, but do not harm animal cells.

Much of the early work on AACs involved Compound 1, in Figure 1, which illustrates the amphiphilic character. This structure is amphiphilic by virtue of the hydrophobic t-butyl group projecting from the bottom of the repeat unit, and a charged amino group (at the top of the repeat unit).

Using this simple chemical scaffold, numerous series of analogs were synthesized as either defined oligomers and small molecules or heterogeneous polymers. Several of these oligomer and polymer series were discovered to have potent antimicrobial activity and high killing selectivity for bacteria versus mammalian cells.

Subsequently, through molecular modeling and chemical elaboration, we were able to improve the biological activities and selectivity of these compounds. Structurally defined oligomers and small molecules are under development for therapeutic applications, whereas the polymers and certain low-cost oligomers are under investigation as materials.

Powerful Antimicrobial Activity

In proof of principle experiments, acrylamide polymers similar in structure to compound 1 were painted onto glass and plastic surfaces at concentrations of 0.01 percent concentration. When exposed to bacteria under typical growth conditions, the coated materials completely inhibited bacterial growth. (See Figure 2.)

Antibacterial activity has also been demonstrated with polyurethane plastic films coated with antimicrobial materials. In one experiment, polyurethane was coated onto a glass slide, and an oligomeric AAC was adsorbed onto the surface at 0.1 percent concentration using dimethyl sulfoxide as the solvent. The resulting slides were then placed in a bacteria-rich nutrient broth for 72 hours to ascertain growth of bacterial colonies. In Figure 3, three photographs show a blank glass slide, a slide coated with polyurethane film alone (control, no polymer), and a polyurethane coated slide with 0.1 percent polymer.