|
Antimicrobial
peptides: A natural alternative to chemical antibiotics and a potential
for applied biotechnology
Sergio
H. Marshall* Gloria
Arenas
A large group of natural compounds exhibiting antimicrobial activity have been isolated from animals and plants during the past two decades. Most of them are either low molecular weight proteins or small peptides ranging from 20 to 80 amino acids in length, which constitute the most diverse and particularly active group. This new generation of native peptide molecules is also known as Anti Microbial Peptides (AMPs). From this diversity, AMPs that are cationic and amphipatic, clearly outstand as the most widespread, and novel classes of peptides with varying chemical propertiescontinue to be isolated from different vertebrate and invertebrate species, as well as from bacteria. Irrespective of their nature, all of them share antimicrobial activity as a common feature, a condition that has led researchers to consider them as "natural antibiotics". This is important since it is now estimated that about half of all bacterial strains found at many medical institutions are resistant to chemical antibiotics. Consequently, the priority for the next decades should be centred in the development of alternative drugs that could allow the proper control of pathogen-caused diseases. Ideally, these molecules should be as natural as possible, with a wide range of action over several pathogens, easy to produce, and hopefully, not prone to induce resistance. In this review we characterize and classify all such molecules known up to date. From eukaryotes we discuss the cecropins, one of the first antibacterial peptide group characterized; the defensins, found in a wide range of organisms; the thionins, exclusively from plants; and other groups derived from functional precursors (histones, pigments, lactoferrin, milk, to name a few). In the latter, a small group of peptides mostly isolated from mammals are the most distinguished. From prokaryotes, the bacteriocins produced by lactic acid bacteria are discussed. How do these peptides act? And why they could be better than chemical antibiotics? The proposal is that because of their amphipatic nature, AMPs interact with the bacterial membranes increasing their permeability "leaking out" the cellular content and as such, impeding the bacteria to develop resistance. The mechanism of action is explained by three different alternatives: 1. Action of their positive charges over anionic lipids of the membrane; 2. Membrane destabilization through lipid displacements due to the drastic changes in the net charge of the composed system, 3. Formation of ion-permeable channels in the lipid bilayers of the target organism. Nonetheless, although a handful of over 1000 different AMPs have been characterized, some peptides do penetrate into cells to exert their action over intracellular molecules. The
potential massive use of these natural compounds is hampered by the
limited amount that can be extracted in vivo as well as a
non-optimal specific activity, which would require huge amounts for
clinical and therapeutical application. Applied biotechnology could
play a pivotal role in the near future to allow easy expression and
large scale purification of these molecules. From a more innovative
point of view, gene amplification and transgenesis seem like feasible
ways, among others, to increase production and enhance specific activity
of selected AMP molecules.
|
|||||||||||
|
Home | Mail to Editor | Search | Archive | ||