Introduction:

Well over 800 different peptides with antimicrobial activity ⁹ have been found in many tissues and cell types of a variety of animal, plant, and invertebrate species ^{1, 5, 10, 11}. Select neuropeptides (e.g., Substance P, enkelytin, Peptide B, Neuropeptide Y, PYY, and skin PYY); peptide hormones (e.g., a MSH, adenoregulin, adrenomedullin AM, proadrenomedullin N-terminal 20 peptide, corticostatin RK-1, neurotensin, and bradykinin); chemokines and cytokines (e.g., MIP3α, CXCL9, -10, and -11, interferon-γ, platelet basic protein, CXCL4, CCL5, and other members of the CC, CXC, CX3C, and C subfamilies); and fragments of larger proteins (e.g., lactoferricin from lactoferrin, casocidin I from human casein, and antimicrobial domain fragments from bovine alpha-lactalbumin, human haemoglobin, lysozyme, and ovalbumin) also are reported to have antimicrobial activity ².

All of these peptides are an abundant and diverse group of molecules with potent, broad-spectrum antimicrobial activity against Gram-negative and Gram-positive bacteria, fungi, and viruses.

“This research identified a new class of host-derived peptide antibiotics as part of the innate immune system that are significantly different from those previously reported.”

Antimicrobial peptides are an abundant and diverse group of molecules that are produced by many tissues and cell types in a variety of invertebrate, plant, and animal species. They are a chemically and structurally diverse and multifunctional group of molecules that are versatile in their mechanisms of microbial killing. They have a variety of applications to prevent or treat infectious disease in humans, animals, and plants; retard contamination of foods; and retard spoilage of processed foods.

In 1996, I entered the field of antimicrobial peptide research when we isolated three small anionic peptides (AP) from sheep lung lavage fluids that were antimicrobial, for ovine pathogens. The peptides, H-GADDDDD-OH, H-GDDDDDD-OH, and H-DDDDDDD-OH, were found in ovine surfactant extracts, bronchoalveolar lavage fluid, and airway epithelial cells. They occurred in mM concentrations, required zinc as a cofactor for antimicrobial activity, and were rapidly antimicrobial against both Gram-positive and Gram-negative organisms.

This research identified a new class of host-derived peptide antibiotics as part of the innate immune system that are significantly different from those previously reported. Antimicrobial anionic peptide (AP)-like molecules were later detected in human BAL fluids and pulmonary epithelia in studies funded by the Cystic Fibrosis Foundation. Such research demonstrated to us that not all antimicrobial peptides kill by inducing lytic pores in microbial membranes (Figure 3).

The diverse mechanisms of antimicrobial activity lead to a number of questions. First, how do these mechanisms relate to applications where antimicrobial peptides are put into substrates or tethered to surfaces?

Alternate mechanisms of antimicrobial activity can explain why many of these peptides retain their specificity and antimicrobial activity when incorporated into thin films, linked to solid phase surfaces, or conjugated to larger carrier molecules ^{3, 4, 6-8}.

Second, can carrier proteins be used to "direct" antimicrobial activity to specific microorganisms in a polymicrobial community? Such activity could target antimicrobial activity towards a specific pathogen in a community of commensal organisms thus eliminating the problems associated with eliminating the entire community of commensals (e.g., oral cavity).

This field is maturing rapidly. The future is promising with additional applications to come! Currently, there are over 202 US patent applications involving antimicrobial peptides.