Antimicrobial Peptides…

Small, But Potent Killers

new approach is The molecular structure of the human antimicrobial peptide, needed, as we Definsin. The red portion denotes Aexplore novel types positively charged amino acids. of antimicrobials for which Green denotes hydrophobic amino the pathogens that currently acids. This characteristic is key to plague us have not yet its destructive capabilities. developed resistance. What sorts of molecules are Perhaps scientists have they? How are they employed overlooked one of nature’s by animals in their defense? As our need for new most potent molecules in the Jay Hardy, CLS, SM (ASCP) arsenal against invasive antibiotics becomes more organisms. pressing, could we design anti-infective drugs based on

Consider that the cornea of the design principles these Jay Hardy is the founder and molecules teach us? CEO of Hardy Diagnostics. the eye of an animal is almost He began his career in always free of signs of microbiology as a Medical infection. The insect Antimicrobial peptides are a Technologist in Santa flourishes without vital component of the innate

Barbara, California. lymphocytes or antibodies. A immune response and are found among all classes of In 1980, he began plant seed germinates manufacturing culture media successfully in the midst of plant and animal life. for the local hospitals. soil microbes. How is this Today, Hardy Diagnostics is accomplished?

the third largest media Powerful Agents of Healing manufacturer in the U.S.

To ensure rapid and reliable What are AMPs? AMPs consist of small turn around time, Hardy proteins with potent broad- Diagnostics maintains six Both animals and plants spectrum antimicrobial

distribution centers, and possess potent, broad- activity. AMPs alter the host produces over 2,700 immune response through products used in clinical and spectrum antimicrobial industrial microbiology peptides (AMPs), which they receptor-dependent laboratories throughout the use to fend off a wide range of interactions and have been world. microbes, including bacteria, shown to be important in such fungi, viruses and protozoa. diverse functions as angiogenesis, wound healing, enter lipid-rich membranes of Bacterial membranes are and chemotaxis. It appears various microbes. Once inside organized in such a way that that AMPs work hand in hand a target membrane, the the outer lipid layer is with other defense peptide kills target cells negatively charged. In mechanisms in the human through diverse mechanisms. contrast, the outer layer of the body such as vitamin D, as we cell membranes of plants and shall see below. Cathelicidins and defensins animals is composed are major groups of epidermal principally of lipids with no AMPs have been AMPs. Decreased levels of net charge. Because AMPs are demonstrated to kill Gram these peptides have been positively charged, they are negative and Gram positive noted for patients with atopic attracted to the negative bacteria (including strains that dermatitis and Kostmann's charge of the microbial are resistant to conventional syndrome, a congenital membrane. This accounts for antibiotics), mycobacteria neutropenia. In addition to the fact that AMPs do not (including Mycobacterium important antimicrobial attack the host tissue tuberculosis), enveloped properties, growing evidence membranes that are rich in viruses, fungi and even indicates that AMPs alter the neutral cholesterol. transformed or cancerous host immune response cells. Unlike the majority of through receptor-dependent How do antimicrobial conventional antibiotics it interactions. peptides actually kill appears as though microbes? Many hypotheses antimicrobial peptides may have been presented, which also have the ability to Methods of Mass include the disruption of the enhance immunity by Destruction microbial membrane functioning as functions and the fatal immunomodulators. Although Antimicrobial peptides have “punching” of holes in the some organisms, such as the exploited a fundamental membrane. human gut commensals, difference in the design of the Lactobacillus spp. and membranes of microbes and Fusobacterium nucleatum, multicellular animals. appear to be resistant to AMPs, this resistance cannot be transferred as we have seen with other antimicrobials.

A Protein Designed for Invasion

These AMPs are usually positively charged and have both a hydrophobic and hydrophilic side that enables the molecule to be soluble in aqueous environments yet have the capability to the However, AMPs are not an tuberculosis. Furthermore, Liu consideration as ‘chemical indestructible super hero, in showed that adding vitamin D condoms’ to limit the spread that some organisms such as to African American serum of sexually transmitted Morganella and Serratia do (African Americans have diseases, including Neisseria not have a sufficient higher rates of TB) gonnorhoeae, Chlamydia, negatively charged lipid dramatically increased human immunodeficiency membrane to be vulnerable to production of these naturally virus (HIV), and Herpes their attack. occurring antibiotics. simplex virus (HSV).

Is Vitamin D an Antibiotic? Could it be that large doses of In addition, it has been found vitamin D could induce an that AMPs can enhance the Recent research shows that increased production of AMPs potency of existing antibiotics vitamin D up-regulates ability to reach therapeutic levels? in vivo, probably by to fight infections by helping Research is currently being facilitating access of produce over 200 conducted to explore this antibiotics into the bacterial antimicrobial peptides, the synergistic partnership of cell, a phenomenon most important of which is vitamin D and AMPs. previously recognized for the cathelicidin. cationic peptide component of Possible Pharmaceutical polymyxin. Applications Conclusion The growing problem of resistance to conventional The fact remains that most antibiotics and the need for animals, including insects and new antibiotics has stimulated creatures like the octopus and interest in the development of starfish, rely heavily on antimicrobial peptides as antimicrobial peptides for human therapeutics. Most defense against microbes, and pharmaceutical effort has do so quite effectively without been devoted to the the help of lymphocytes, a The sunshine vitamin plays an important role in the stimulation of development of topically thymus, or antibodies. AMPs, which are essential to the applied agents, such as the fight against disease. AMP known as the magainin These mechanisms can be analogue pexiganan. effectively exploited to Dr. Philip Liu and colleagues Currently the strategy is to develop new therapeutic at UCLA, showed that develop topical agents largely modalities in order to keep vitamin D might be, in effect, because of the relative safety one step ahead of increasingly a potent antibiotic. Vitamin D of topical therapy and the resistant microbes. increases the body's uncertainty surrounding the production of naturally long-term toxicology of any Even though AMPs have been occurring AMPs, which are new class of drug studied for 20 years, there is produced in numerous cells in administered systemically. still much to discover as this the human body where they exciting new area of directly and rapidly destroy The broad antimicrobial microbiology unfolds. the cell walls of viruses and spectrum of antimicrobial bacteria, including peptides positions them for Jay Hardy, CLS, SM (ASCP) Santa Maria, CA