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What's the next step in Fighting Antibiotic-Resistant Bacteria? Nanotechnology

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In Brief

Over the last hundred years, antibiotics have been central to the extraordinary rate of improvement in medical technology. From swiftly curing basic infections to raising the rate of survival after invasive surgical procedures, they have given humanity superior life expectancy and overall health today than at any point in the history of civilization. As many know, however, excessive and improper prescription of antibiotics to treat illness has led to the appearance of antibiotic-resistant bacteria. In the search for novel approaches to fighting this bacteria, nanotechnology has come into increasing use.

Inhospitable Surfaces

One method with widespread applicability is the creation of antimicrobial surfaces which limit initial bacterial attachment, as opposed to sanitizing bacteria after they appear. This idea would most commonly be used on surfaces inside the human body, where normal sanitizing methods (ie. use of 70% ethanol or isopropanol alcohol) are not practical. Nanotechnology is used to create surfaces on implants which mimic natural nanoscale topographies, such as those of lotus leaves, shark skin, or dragonfly wings, which have shown to possess antimicrobial/anti-fouling effects.

 

Alternatively, nanotechnology can be used to create hydrophobic surfaces, which minimize the ability of all moisture to adhere to the implant. Given the regular use of implants such as pacemakers, any use of nanotechnology along these lines should have an immediate impact on medical outcomes.

 

Taking Cues From Nature 

Nanofibers derived from biological sources—e.g. chitosan, cellulose, or antimicrobial proteins are another type of nanoparticle with medical applications.

  • Chitosan nanofibers have been a popular subject of study due to the ease and lack of expense in acquiring them, as they are a common waste product of shellfish. Chitosan surfaces do not limit bacterial attachment; rather, when bacteria adhere to chitosan, the cell membrane of the bacteria is disrupted, leading to leakage of cell components. Additionally, chitosan has the ability to interact with the DNA of bacteria, inhibiting both DNA transcription and protein synthesis. However, obtaining nanofibers is normally done via electrospinning, which is challenging due to the limited solubility of chitosan in common organic solvents.
  • Cellulose, derived from plant cell walls and vegetable fibers, is Earth's most common natural polymer. Cellulose nanofibers are easier to obtain through electrospinning, and as such are routinely used for antimicrobial purposes. Cellulose alone does not work against bacteria; it must have an active agent, such as sorbic acid, benzalkonium chloride, or copper or silver chloride nanoparticles incorporated into the nanofibers for them to be effective.
  • Antimicrobial peptides are proteins that are part of the native immune response found in all organic classes - including plants, animals, viruses, and bacteria. The Antimicrobial Peptide Database currently lists over two thousand such peptides. AMPs must be delivered in a way that helps maintain their antimicrobial efficacy. As with cellulose and its need for an active agent, nanofibers have recently been used as carriers for AMPs. The use of nanofibers can substantially impact the antimicrobial activity of an AMP. Some combinations can render the AMP effectively inactive, but in certain cases, the AMP's efficacy can be enhanced. One study showed the specific combination of colistin sulfate and PVA nanofibers improved the antimicrobial activity of the colistin sulfate by five to six times. (An article from MIT about a study by their researchers on this topic can be found here).

 

Synthesizing Solutions 

Another form of nanotechnology of note is the use of synthetic nanofibers with biologically originated antimicrobial compounds. The compounds include propolis, a resin-like substance created by honeybees, and essential oils extracted from plants.

  • The antibacterial capacity of propolis has been well-studied and is attributed to the phenolic compounds in its flavonoid fractions. Electrospun fibers of propolis and polyurethane have shown the ability to inhibit E. coliS. aureusStaphylococcus epidermidis, and Proteus mirabilis. The use of propolis is challenging due to the difficulty of maintaining uniformity or consistency in its inhibitory effects, as the composition varies according to local climate and season. However, should this problem be solved, the technology to spin the nanofiber mats required for its use is proven.
  • Essential oils, more commonly known for their aromatic qualities, are also concentrated hydrophobic liquids. The compounds present in essential oils can permeate bacteria cell membranes, leading to proton depletion, disruption of ATP synthesis, and, in some cases, cell lysis. Essential oils have a centuries-old history of fighting infections and are shown to be more difficult for bacteria to resist than modern antibiotics. The effort necessary to incorporate essential oils into nanofiber mats kept the two from being paired until 2009, but studies have shown tremendous promise; in one such study, cinnamaldehyde combined with chitosan nanofibers killed 80% of E. coli bacteria exposed to it within thirty minutes.

Summary

Despite the challenges created by the inappropriate prescribing of antibiotics, nanotechnology is proving it could be a promising next step in managing the risk of bacterial infections.

 

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