|AMP > Discussion > Relevancy of AMPs:
Is there more to come?
Although at present AMPs are believed to exerttheir primary activity on bacterial membranes, new evidence is suggesting that AMP activity might be broader, including selective inhibition of intracellular targets . It is thought that cationic peptides might induce genomic responses in bacteria treated with AMPs, in addition to any lethal effect on the bacterial membrane. This appears to be the case, as recently demonstrated (Hong et al. 2003) .These authors have shown that the transcription profiles of at least 26 Escherichia coli genes change specifically and significantly after exposure to lethal and sub lethal concentrations of Cecropin A, an emblematic cationic peptide. Moreover, half of these transcripts corresponded to proteins of unknown function, which makes these observations quite intriguing.
Now, regarding the wide
variety and diverse classes of natural peptides, we must add
necessarily, the processing alternatives, which are slowly being
reported that might make these molecules incommensurable, approaching
the diversity of immunoglobulins. The case of lactoferricin-C,
generated as a functional internal domain of caprine lactoferrin in a
manner mimicking the generation of inteins (selfish DNA elements
inserted in-frame and translated together with their host proteins: (http://bioinfo.weizmann.ac.il/~pietro/inteins),
opens a new and broad area of research. Something similar occurs with
milk-derived compounds, where it is clear that milk contains a group of
proteins, which perform a protective function. These proteins harbor in
their primary sequence, peptides that are inactive in the parent protein
and that are released during gastrointestinal digestion or food
processing (Yamauchi, 1992). In contrast,
the generation of thrombocidin, arising from carboxy-terminal deletions
of key neuthrophil- and connective tissue-activating peptides in humans,
broadens the spectrum of alternative for processing associated with the
generation of AMPs. Additionally, slight variations in the structure of
preexisting peptides might broaden their potential as AMPs. A good
example is that of histatin-5, a naturally occurring anti-fungal
peptide in human saliva, which presents at least two variants (dhvar4
and dhvar5) displaying increased anti-microbial activity by subtle
changes in their amphipathicity, a good indicator of membrane
destroying activity, which allows them to be internalised showing
a more destructive effect on mitochondria than on external membranes .
Therefore, it is reasonable to think that a number of existing
functional proteins, unrelated to immune responses, might contain
potential and fully active AMPs This is a complementary strategy to
that of natural anti-microbial peptides, which by themselves might
adjust to potential bacterial adaptations to counteract their
pathogenicity. This is only the tip of the iceberg in this
appealing topic. The recent proposalthat antibody multi specificity can
be mediated by conformational diversity of pre existing isomers to
increase the effective size of the antibody repertoire is perfectly
applicable to understand diversity of existing AMPs as well as the
potential of those derived from multiple and heterogeneous type
of precursors.Only time will verify these assumptions(James et al. 2003).
R.W.; SHCHEPETOV, M.; WEISER, J.N.; AXELSEN, P.H. Transcriptional
profile of the Escherichia coli response to the antimicrobial
insect peptide cecropin A. Antimicrobial Agents and Chemotherapy,
2003, vol. 47, no. 1, p. 1-6.
K. Biologically functional proteins of milk and peptides derived
from milk proteins. Bulletin IDF, 1992, vol. 272, no. 1,
C.; ROVERSI, P. and TAWFIK, D.S. Antibody multispecificity mediated
by conformational diversity. Science, 2003, vol. 299, no.