Bacterial cell wall compounds as Promising targets of antimicrobial agents I. Antimicrobial peptides and lipopolyamines
2012
The first barrier that an antimicrobial agent must overcome when interacting with its target is the microbial cell
wall. In the case of Gram-negative bacteria, additional to the cytoplasmic membrane and the peptidoglycan layer, an outer
membrane (OM) is the outermost barrier. The OM has an asymmetric distribution of the lipids with phospholipids and
lipopolysaccharide (LPS) located in the inner and outer leaflets, respectively. In contrast, Gram-positive bacteria lack OM
and possess a much thicker peptidoglycan layer compared to their Gram-negative counterparts. An additional class of amphiphiles
exists in Gram-positives, the lipoteichoic acids (LTA), which may represent important structural components.
These long molecules cross-bridge the entire cell envelope with their lipid component inserting into the outer leaflet of the
cytoplasmic membrane and the teichoic acid portion penetrating into the peptidoglycan layer. Furthermore, both classes of
bacteria have other important amphiphiles, such as lipoproteins, whose importance has become evident only recently. It is
not known yet whether any of these amphiphilic components are able to stimulate the immune system under physiological
conditions as constituents of intact bacteria. However, all of them have a very high pro-inflammatory activity when released
from the cell. Such a release may take place through the interaction with the immune system, or with antibiotics
(particularly with those targeting cell wall components), or simply by the bacterial division. Therefore, a given antimicrobial
agent must ideally have a double character, namely, it must overcome the bacterial cell wall barrier, without inducing
the liberation of the pro-inflammatory amphiphiles. Here, new data are presented which describe the development and use
of membrane-active antimicrobial agents, in particular antimicrobial peptides (AMPs) and lipopolyamines. In this way,
essential progress was achieved, in particular with respect to the inhibition of deleterious consequences of bacterial infections
such as severe sepsis and septic shock.
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