Apidaecin-type peptides:
biodiversity, structure-function relationships and mode of
action
Apidaecins (apidaecin-type peptides) refer to
a series of small, proline-rich (Pro-rich), 18- to 20-residue
peptides produced by insects. They are the largest group of
Pro-rich antimicrobial peptides (AMPs) known to date.
Structurally, apidaecins consist of two regions, the conserved
(constant) region, responsible for the general antibacterial
capacity, and the variable region, responsible for the
antibacterial spectrum. The small, gene-encoded and unmodified
apidaecins are predominantly active against many gram-negative
bacteria by special antibacterial mechanisms. The mechanism of
action by which apidaecins kill bacteria involves an initial
non-specific binding of the peptides to an outer membrane (OM)
component. This binding is followed by invasion of the
periplasmic space, and by a specific and essentially
irreversible combination with a receptor/docking molecule that
may be a component of a permease-type transporter system on
inner membrane (IM). In the final step, the peptide is
translocated into the interior of the cell where it meets its
ultimate target. Evidence that apidaecins are non-toxic for
human and animal cells is a prerequisite for using them as
novel antibiotic drugs. This review presents the biodiversity,
structure-function relationships, and mechanism of action of
apidaecins.
Li WF, Ma GX, Zhou XX. Peptides. 2006
Sep;27(9):2350-9
Pro-rich antimicrobial peptides
from animals: structure, biological functions and mechanism of
action
Pro-rich antimicrobial peptides are a group
of linear peptides of innate immunity isolated from mammals
and invertebrates, and characterised by a high content of
proline residues (up to 50%). Members of this group are
predominantly active against Gram-negative bacterial species
which they kill by a non-lytic mechanism, at variance with the
majority of the known antimicrobial peptides. Evidence is
accumulating that the Pro-rich peptides enter the cells
without membrane lysis and, once in the cytoplasm, bind to,
and inhibit the activity of specific molecular targets
essential to bacterial growth, thereby causing cell death.
This mode of action makes these peptides suitable for drug
development efforts. In addition to antibacterial action,
PR-39, one of the better characterised Pro-rich peptides from
mammals, exerts other potentially exploitable biological
activities, such as induction of syndecan expression in
mesenchymal cells and inhibition of the NADPH oxidase activity
of neutrophils, suggesting a role of this peptide in wound
repair and inflammation. PR-39 also exerts a protective effect
in various animal models of ischemia-reperfusion injury,
preventing the post-ischemic oxidant production, and is a
potent inducer of angiogenesis both in vitro and in vivo.
Although the physiological relevance of all these effects has
not yet been established, the above observations underscore
the therapeutic potential of this peptide in a number of
complex processes such as inflammation, wound repair,
ischemia-reperfusion injury, and angiogenesis.
Gennaro R, et al. Curr Pharm Des. 2002;8(9):763-78.
