Antimicrobial Peptides (Tortora)

Although fairly recently discovered, antimicrobial peptides (AMPs) may be one of the most
important components of innate immunity (sec also Chapter 20, pages 578 to 579).
Antimicrobial peptides arc short peptides that consist of a chain of about 12 to 50 amino acids
synthesized on ribosomes. They were first discovered in the skin of frogs, the lymph of insects,
and human neutrophils; to date, over 600 AMPs have been discovered in nearly all plants and
animals. AMPs have a broad spectrum of antimicrobial activities, including activity against
bacteria, viruses, fungi, and eukaryotic parasites. Synthesis of AMPs is triggered by protein and
sugar molecules on the surface of microbes. Cells produce AMPs when chemicals in microbes
attach to Toll-like receptors (see page 458). The modes of action of AMPs include inhibiting cell
wall synthesis; forming pores in the plasma membrane, resulting in lysis; and destroying DNA
and RNA. Among the AMPs produced by humans are dermcidin, produced by sweat glands;
deJensins and cathelicidirls, produced by neutrophils, macrophages, and epithelium; and
thrombocidin, produced by platelets. Scientists arc especially interested in AMPs for a number
of reasons. Besides their broad spectrum of activity, AMPs have shown synergy (working
together) with other antimicrobial agents, so that the effect of them working together is
greater than that of either working separately. AMPs are also very stable over a wide range of
pH. What is particularly significant is that microbes do not appear to develop resistance even
though the microbes are exposed to them for long periods of time. In addition to the killing
effect of AMPs, they also participate in a number of other immune functions. For example,
AMPs can sequester the LPS shed from gram-negative bacteria. Recall that the lipid A
component of the LPS functions as an endotoxin and is responsible for the symptoms
associated with infection by gram-negative bacteria (septic shock). AMPs have been found to
vigorously attract dendritic cells, which destroy microbes by phagocytosis and initiate an
adaptive immune response. AM Ps have also been shown to recruit mast cells, which increase
blood vessel permeability and vasodilation. This brings about inflammation, which destroys
microbes, lim its the extent of damage, and initiates tissue repair.