Advances in antimicrobial peptide immunobiology

Abstract

Antimicrobial peptides are ancient components of the innate immune system and have been isolated from organisms spanning the phylogenetic spectrum. Over an evolutionary time span, these peptides have retained potency, in the face of highly mutable target microorganisms. This fact suggests important coevolutionary influences in the host-pathogen relationship. Despite their diverse origins, the majority of antimicrobial peptides have common biophysical parameters that are likely essential for activity, including small size, cationicity, and amphipathicity. Although more than 900 different antimicrobial peptides have been characterized, most can be grouped as belonging to one of three structural classes: (1) linear, often of alpha-helical propensity; (2) cysteine stabilized, most commonly conforming to beta-sheet structure; and (3) those with one or more predominant amino acid residues, but variable in structure. Interestingly, these biophysical and structural features are retained in ribosomally as well as nonribosomally synthesized peptides. Therefore, it appears that a relatively limited set of physicochemical features is required for antimicrobial peptide efficacy against a broad spectrum of microbial pathogens. During the past several years, a number of themes have emerged within the field of antimicrobial peptide immunobiology. One developing area expands upon known microbicidal mechanisms of antimicrobial peptides to include targets beyond the plasma membrane. Examples include antimicrobial peptide activity involving structures such as extracellular polysaccharide and cell wall components, as well as the identification of an increasing number of intracellular targets. Additional areas of interest include an expanding recognition of antimicrobial peptide multifunctionality, and the identification of large antimicrobial proteins, and antimicrobial peptide or protein fragments derived thereof. The following discussion highlights such recent developments in antimicrobial peptide immunobiology, with an emphasis on the biophysical aspects of host-defense polypeptide action and mechanisms of microbial resistance.

The proteolytically stable peptidomimetic Pam-(Lys-βNSpe)6-NH2 selectively inhibits human neutrophil activation via formyl peptide receptor 2

“…A c c e p t e d M a n u s c r i p t 5 a number of these peptides exhibit both direct microbicidal activity and potent immunomodulatory functions via interaction with various immune-competent cells such as neutrophils [10][11][12]. Being among the first cells to be recruited to the site of infection, neutrophils are important early effector cells of the innate immune system.…”

Host Defense Peptides in Wound Healing

“…Microorganisms have also developed ways to escape direct killing by human host defense peptides (171)(172)(173)(174), which emphasizes their important and ancient role in the innate immune system (172). However, resistance mechanisms are generally related to the direct killing of bacteria and are not comparable to the resistance mechanisms of conventional antibiotics.…”

Defensive Effects of Human Antimicrobial Peptide .ALPHA.-Defensins against Enterococcus faecalis

“…8) However, it should be noted that human pathogens may resist the bactericidal actions of AMPs through modification of the phospholipid composition in the cell membrane, 9) production of peptidases that can degrade AMPs, 10,11) and expression of the AMP efflux pumps. 9) Enterococcus faecalis (E. faecalis) is a Grampositive bacterium inhabiting the gastrointestinal tracts of humans and other mammals, 12,13) and this species is also isolated from some probiotic foods. 14) Like other enterococci, E. faecalis causes life-threatening nosocomial infections because of its high multidrug resistantce.…”