Super-Cationic peptides: insights on their antimicrobial action

Programa de Doctorat en Medicina i Recerca Translacional [eng] Bacteria have been to the human civilization a threat as well as an ally, since the beginning of time. The introduction of antibiotics into clinics to treat infections was one of the best medical achievements ever accomplished. However, the increase of antimicrobial resistance (AMR) as well as the failure to develop new antibiotics is a cause of much concern, and is essential to create new strategies of development in order to fight this global threat. Bacterial cell membranes are a key factor in the emergence and evolution of resistant bacteria, due to their capacity to interact with other organisms, the environment or both. Therefore, the study of the physical and chemical properties of biological membranes is essential to understand their role in resistance. One path to develop new strategies and create new antimicrobial agents to address the global threat of resistant bacteria is the synthesis of new compounds as an alternative therapy, like synthetic antimicrobial peptides (AMPs). In this context, the active exploration of peptides from the new AMP family, named the Super-Cationic peptide dendrimers (SCPDs) was carried out. HYPOTHESIS: The main hypothesis of this thesis is that synthetic peptides may have antimicrobial properties against clinical bacterial strains, and may provide weapons to treat infections caused by multidrug-resistant strains. A deep research of the mechanisms underlying antimicrobial action should be carried out. OBJECTIVES: The main objective of this thesis is to determine the antimicrobial properties of synthetic peptides from a new AMP family, SCPDs, specifically the peptide G1OLO-L2OL2. The secondary objectives of this thesis are divided in three parts: First, finding the eventual target and interactions those peptides may have with the bacteria, particularly its possible interaction with the bacterial cell membrane. Second, to determine the cytotoxicity these molecules may have over eukaryotic cells. And third, to observe the effect these molecules may have on the bacteria, the cell membranes and on artificial membranes by means of atomic force microscopy (AFM). [spa] Las bacterias han sido desde el principio de los tiempos una amenaza y un aliado para la civilización humana. La introducción de los antibióticos en la clínica para tratar infecciones fue uno de los mejores logros médicos jamás logrados. No obstante, el aumento de las resistencias a los antimicrobian