Despite tremendous strides in the development of anti-infectives, most experts believe they are losing the war against microbes. Resistance to antimicrobial agents has been magnified to some degree in nearly every strain of bacteria pathogenic to humans and animals.
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Explore This IssueApril/May 2007
Methicillin-resistant Staphylococcus aureus (MRSA), already common in hospitals, is responsible for many untimely deaths. In 2002, this bacterium killed more than 800 Americans. That’s more lives than claimed by SARS and avian influenza combined. Almost weekly, one reads about outbreaks of “super-bugs” with resistance to vancomycin, which –until recently – was considered the antibiotic of last resort.
The increased use of antibiotics in food animals is a potential source of microbial resistance with immediate impact on public health. According to data from the Centers for Disease Control and Prevention (CDC), contaminated food causes 76 million illnesses, 325,000 hospitalizations and 5,000 deaths in the United States each year. Although more than 200 known diseases are caused by contaminated food, Toxoplasma, Salmonella and Listeria cause more than three-quarters of foodborne illnesses. The latter of the two are two of the 10 most common food pathogens. Although many of these organisms originate from the environment, the carry-over of resistant pathogens from slaughtered animals is always a concern.
Meat processors are not alone in the fear of foodborne. Recent recalls of spinach, high-end pet foods, peanut butter and baby food – in addition to hamburgers and other meat products –underscore the urgency of reducing sources of contamination to the greatest possible extent.
Novel antimicrobial materials, however, could revolutionize manufacturing of products that come into contact with foods during production, processing and storage. These products – amphiphilic antimicrobial compounds (AACs) –are chemical mimics of host defense peptides, molecules that occur naturally in higher organisms to ward off infection. AACs are available in small-molecule and polymeric format and suitable for use as both antimicrobial therapies and germicidal materials, respectively.
AACs have unique properties, which set them apart from traditional antimicrobial molecules and materials, including:
- A novel mechanism of action that makes development of bacterial resistance unlikely;
- Potent, ultra-broad spectrum activity against more than 150 Gram-positive and Gram- negative bacteria;
- Unlike many antibiotic classes, AACs are bactericidal, not simply bacteristatic;
- Faster acting than many antimicrobials, with killing times measured in seconds to minutes;
- Straightforward manufacturing through known chemical and polymer synthesis;
- Active against drug-resistant bacteria, including clinical isolates of multiple vancomycin- and methicillin-resistant strains;
- Small-molecule AACs have shown excellent anti-microbial activity in animal studies.
Primitive life forms, such as molds, secrete defense compounds like penicillin to protect themselves from bacteria. Multi-cellular organisms, in particular mammals, possess a more complex, first-line immunity against bacterial infections. Host defense peptides are part of the non-humoral (that is, not involving antibodies) response that keep humans from rapidly succumbing to infections.
Biologists have discovered many different classes of natural host-defense peptides, most containing 20 to 40 amino acids. Although these molecules possess a diverse array of amino acid sequences, their physicochemical properties are similar. All are amphiphilic, meaning they exhibit affinity for both charged/polar and uncharged/non-polar environments. This property, rather than amino acid sequence, believed to be responsible for host defense peptides’ antimicrobial activity. Among the most common and well-studied antimicrobial peptides are the cationic, amphiphilic alpha helices, including the cecropins, magainins and many others.
AACs are designed to mimic the amphiphilic structure of the host defense proteins, but with completely synthetic, non-peptide backbones and, for therapeutic AACs, in small-molecule format. AACs directly cause bacterial cell membranes to rupture, a mechanism that is unique among known antimicrobial compounds. For this reason, antimicrobial agents based on specific compound designs will not engender bacterial resistance.
Although sanitation in food processing is achieved principally through cleaning, the effect of materials used in food-processing surfaces, vessels and implements can be significant. Generally, bacteria have greater difficulty clinging to and persisting on smooth surfaces than on rough ones. Thus many food processing-surfaces particularly those made from metals, are polished to reduce surface roughness.