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The Role of Antimicrobial Peptides in Animal Defenses
Pages 105-110

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From page 105...
... , by a regulatory pathway similar to that used by the mammalian immune system, involving Toll receptors and the transcription factor NAB (24. The Nature of Cationic Antimicrobial Peptides We use the term (cationic)
From page 106...
... Such a mechanism elicits an immediate antimicrobial response to the same microorganisms that have had contact with the epithelial cells, and these responses are related to, but completely independent of, the leukocytedependent immune defense mechanisms. Other obvious differences between the cationic antimicrobial peptide response and the immune response in animals are the highly specific nature of immune responses, the relative slowness of immune responses because of the requirement for clonal cell expansion, and the self vs.
From page 107...
... It was also possible to assess binding of cationic antimicrobial peptides to the Gram-positive surface molecule LTA by using a variation of the dansyl polymyxin displacement assay that is used to assess LPS binding (43~. LTA, like LPS, has both a polyanionic and lipidic nature, and thus was able to interact with dansyl polymyxin and cationic peptides, although the kinetics of binding indicated a lower affinity for binding to LTA compared with LPS.
From page 108...
... To investigate whether cationic antimicrobial peptides might influence sepsis through a novel mechanism involving direct interaction with macrophage cells, we chose the peptide CEMA, a peptide that becomes or-helical on contact with membranes (45~. Although it is derived from insect peptides, it is a paradigm for this class of peptides and has both strong antimicrobial activity against Gram-negative bacteria and good antiendotoxic activity both with cultured macrophages and in mouse models (38~.
From page 109...
... Cationic antimicrobial peptides have many of the desirable features of a novel antibiotic class (6~. In particular, they have a broad spectrum of activity, kill bacterial rapidly, are unaffected by classical antibiotic resistance mutations, do not easily select antibiotic resistant variants, show synergy with classical antibiotics, neutralize endotoxin, and are active in animal models.
From page 110...
... Thus cationic antimicrobial peptides are not only important components of the innate defenses of all animals against infections, but synthetic variants thereof hold great potential as a weapon against antibiotic-resistant bacteria. The great sequence and structural diversity offered by peptides (i.e., 20 possible amino acids in each position)


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