Estudio de las interacciones diferenciales de péptidos antimicrobianos sobre membranas modelo de composición variable : un enfoque computacional mediante simulaciones de dinámica molecular
The antimicrobial peptides (AMPs) are molecules of the innate immune system virtually present into the three domains of life, being part of the oldest defense strategies from an evolutionary point of view. As a general mechanism, the AMPs act by increasing lipidic membrane permeability reaching to p...
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| Formato: | Tesis doctoral acceptedVersion |
| Lenguaje: | Español |
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Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica
2020
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| Acceso en línea: | http://repositoriouba.sisbi.uba.ar/gsdl/cgi-bin/library.cgi?a=d&c=posgraafa&cl=CL1&d=HWA_6729 https://repositoriouba.sisbi.uba.ar/gsdl/collect/posgraafa/index/assoc/HWA_6729.dir/6729.PDF |
| Aporte de: |
| Sumario: | The antimicrobial peptides (AMPs) are molecules of the innate immune system virtually present into the three domains of life, being part of the oldest defense strategies from an evolutionary point of view. As a general mechanism, the AMPs act by increasing lipidic membrane permeability reaching to pore formation or even to a total disintegration of the bilayer. As AMPs do not act against specific membrane receptors but the bilayer itself is the target, they have been proposed as novel antibiotic therapies. However, each peptide can act by different molecular mechanisms, as well as the microorganisms can have different grades of vulnerability to the AMP action. Taking this into account, the lipid variability can allow the modelling and differentiation of eucariotic and procariotic cells, gram positive and gram negative cells, or even different but very related strains of probiotic bacteria.
In order to study how lipidic variability can act as AMP resistance mechanism, the molecular dynamics simulations (MD) allow to study deeply the system interactions at a molecular level by a computational approach. In the present thesis, the AMPs way of action of anuran peptides against model membrane derived from strains of probiotics will be studied by using MD technics combined with dye-release and fluorescence microscopy experiments. The ability of some cells to resist the action of different antimicrobial agents through a passive, psychical and generic mechanism like membrane composition is a key aspect to
study the AMPs and to develop them as new antimicrobial therapies, and also in order to develop better probiotc foods. |
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