Abstract
The increase in super-resistant bacteria to traditional antibiotics is a common problem nowadays mainly due to the abusive use of these drugs. Nearly 20 years ago a new class of molecules, the antimicrobial peptides (AMPs), was found to have potent microbicidal properties. The AMPs have a non-specific, fast and lethal mechanism of action against microorganisms, causing cell death by disrupting the cell membrane. This occurs due to the mechanism of pore formation (Barrel-stave, toroidal and carpet models) or transport of peptide across the membrane resulting in its binding to intracellular molecules and inhibiting cell wall biosynthesis, DNA, RNA and protein synthesis. The toxicity of AMPs is small because of their physical chemical properties (they are mainly cationic), which usually allows to distinguish between eukaryotic cells (zwitterionic) and bacterial cells (anionic). This project aims to determine the mechanism of action of two cyclic AMPs, labaditin, a hydrophobic peptide obtained by the binding of its N- and C- terminal regions and active against Gram-positive Streptococcus mutans; and bactenecin a cationic peptide cyclized via a disulfide bridge and active against Burkholderia pseudomallei, causative agent of melioidosis. Cyclic peptides have greater conformational restriction, are more resistant to proteolytic degradation and often have greater antibacterial activity than their linear analogues. Thus, using Langmuir monolayers as model systems of biomembranes and in situ characterization techniques such as PM- IRRAS and Brewster angle microscopy (BAM), this project aims to unravel the mechanism of action of these compounds correlating their structure (linear or cyclic) with their antimicrobial activity. Also, we aim to evaluate the ability of the peptide L and D, ±-Labaditin, similar to Gramicidin, in forming nanotubes with high effectiveness against bacteria, but low hemolytic activity.
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