7.6.6: Antimicrobial Peptides

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Antimicrobial peptides exhibit cytotoxic activity against all microbes.

Learning Objectives

Discuss the structure, mechanism, and targets of antimicrobial peptides

Key Points

Antimicrobial peptides (AMPs) are a unique and assorted group of molecules produced by living organisms of all types, considered to be part of the innate immunity of a host.
These peptides demonstrate potent antimicrobial activity and are rapidly mobilized to neutralize a broad range of microbes, such as viruses, bacteria, protozoa, and fungi.
The ability of these natural molecules to kill multidrug-resistant microorganisms has gained them considerable attention and clinical interest.

Key Terms

neutropenia: A hematological disorder characterized by an abnormally low neutrophil count.
atopic dermatitis: An atopic, hereditary, and non-contagious skin disease characterized by chronic inflammation of the skin.

A first line of defense against pathogenic insult is called the innate immune system, which is followed by acquired immune responses associated with the activation of T and B cells aimed against specific antigens. In contrast to the clonal, acquired adaptive immunity, endogenous peptide antibiotics or antimicrobial peptides provide a fast and energy-effective mechanism as front-line defense.

Figure: **Various AMPs**: These are various antimicrobial peptide structures.

Antimicrobial peptides (AMPs) are small molecular weight proteins with broad spectrum antimicrobial activity against bacteria, viruses, and fungi. They are classified on the basis of their structure and amino acid motifs. Peptides of the defensin, cathelicidin, and histatin classes are found in humans. These evolutionarily conserved peptides are usually positively charged and have both a hydrophobic and hydrophilic side that enables the molecule to be soluble in aqueous environments yet also enter lipid-rich membranes. Once in a target microbial membrane, the peptide kills target cells through diverse mechanisms. AMPs secrete lytic enzymes, nutrient-binding proteins or contain sites that target specific microbial macromolecules.

Cathelicidins and defensins are major groups of epidermal AMPs. Decreased levels of these peptides have been noted for patients with atopic dermatitis and Kostmann’s syndrome, a congenital neutropenia. AMPs have proven effective against multidrug-resistant microbes. In addition to important antimicrobial properties, growing evidence indicates that AMPs alter the host immune response through receptor-dependent interactions. AMPs have been shown to be important in such diverse functions as angiogenesis, wound healing, cytokine release, chemotaxis, and regulation of the adaptive immune system. These peptides qualify as innovative drugs that might be used as antibiotics, anti-lipopolysaccharide drugs, or modifiers of inflammation reactions.