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 et al. Peptides. 2006 Sep;27(9):2350-9
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 et al. Curr Pharm Des. 2002;8(9):763-78.
