Evaluating and enhancing the activities of novel antimicrobials: Biomimetics, nanotechnology and natural compounds

The recent finding as to the common distribution of antimicrobial peptides in multicellular organisms and their essential role in innate defenses has uncovered numerous possibilities for novel therapeutics. Despite the diversity of these peptides among organisms, investigations have revealed surprising similarities regarding their structure and their antimicrobial function. The insights gained from studies on antimicrobial peptides have provided new strategies and templates for the development and design of novel biomimetics that may be used in therapeutic, pharmaceutical and food applications. It is these features that are being used in the design of antimicrobially active peptide mimics in polymer and small molecule forms, some of which were investigated here for their broad spectrum activity alone and in combination with functional food ingredients (flavor and aroma compounds) capable of enhancing their activities. These novel combinations could be beneficial for targeted antimicrobial applications. The multicomponent systems developed here combine multiple functionalities -- the abilities of the biomimetic polymers to breach the gram-negative outer membrane and the activities of both components against the cell membrane, and possible targets within the cytoplasm. Because they act on the conserved structure of the cell membrane, these treatments may be difficult to surmount via developed resistance. The research reported here bridges the fields of not only polymer chemistry and microbiology, but also of natural products. As an example, the functional food ingredients used to enhance biomimetic polymer activities were sesquiterpenoids, a class of naturally occurring terpenes that are found in plants where they serve as defensive agents. These compounds, including bisabolol, farnesol and nerolidol have previously been shown to enhance the activities of traditional antimicrobials such as antibiotics (Brehm-Stecher and Johnson, 2003). Their additional ability to dramatically enhance the activities of biomimetic antimicrobial polymers was demonstrated in the present work.;Additional antimicrobial approaches were examined in this work, including the use of essential oils and metal nanoparticles. These compounds, either alone or in combination with enhancing compounds, were investigated with the aim of developing additional multicomponent antimicrobial systems. While essential oils have been used since ancient times for their antimicrobial properties, their use in some applications has been limited due to their strong odors and lack of effective activity at organoleptically acceptable levels. As a result, methods capable of enhancing their antimicrobial activities, especially in complex matrices, could be key to their advantageous use in food and clinical applications. Here, several different essential oils were combined with the polyionic compounds sodium polyphosphate and polyethylenimine and the activities of these systems were examined against a range of human pathogens. These polyions were found to be capable of potentiating the antimicrobial activities of the oils, allowing their effective use at lower levels.;Metals have also been shown to be broad-spectrum antimicrobial agents in both their ionic and macrometallic forms. While these forms have been used for millennia as antimicrobials, little is known about the activities of these metals in nanoparticulate form, an area of great interest given the rapid growth of the nanotechnology sector. Therefore, a series of metal nanoparticles, including several novel alloys, were evaluated for their antimicrobial activities and for their physical (binding) interactions with microbial cell surfaces. Results from this work suggest the potential for using commercial metal nanoparticle catalysts as novel antimicrobial compounds. These could be valuable as components of antimicrobially active surfaces or therapeutics, once potentially limiting safety issues of particle migration and toxicity are addressed.;Taken together, physical or chemical methods for enhancing the activities of core antimicrobials as diverse as biomimetic polymers, metal nanoparticles and essential oils or other natural compounds could provide beneficial strategies for developing effective multi-agent systems having enhanced antimicrobial properties. The resulting systems may find advantageous use in applications as diverse as food safety, environmental sanitation or clinical therapeutics.