Publication: Análisis estructural de la proteína GAPDH de bacterias patógenas Gram-positivas y su función como factor de inmunoevasión
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2018-09-18
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Universidad Complutense de Madrid
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Abstract
Atopobium vaginae es una bacteria Gram-positiva de la familia Corynebacteriaceae, con forma de coco alargado, anaerobia facultativa, aislada inicialmente a partir de una muestra vaginal. Esta bacteria es la responsable de alrededor del 80% de los casos de vaginosis bacteriana en humanos junto a Gardnerella vaginalis, pudiendo desencadenar complicaciones obstétricas, así como problemas en el embarazo y predisposición a otras infecciones oportunistas. Dado que el tratamiento estándar contra la vaginosis bacteriana (siete días tomando dos veces 400 mg de metronidazol) no es eficaz ni duradero, recidivando en el 30% de los casos, es importante encontrar nuevos compuestos antibacterianos que la erradiquen.Como A. vaginae forma biopelículas con G. vaginalis, su nicho es anaerobio y no oxida del todo la glucosa, dependiendo en gran medida de la glicólisis para la obtención de energía. Durante la primera fase de ruta glicolítica la célula consume dos moléculas de ATP por cada glucosa, mientras que durante la segunda fase se producen cuatro moléculas de ATP y dos de NADH, creando un balance neto de dos moléculas de ATP y dos de NADH. La enzima Gliceraldehído 3-fosfato deshidrogenasa (GAPDH) se encarga de transformar el gliceraldehído 3-P en 1,3-bis-fosfoglicerato usando NAD+ como cofactor, consumiendo una molécula de fosfato inorgánico y generando una molécula de NADH. Esta es la primera reacción de la segunda fase de la glicólisis, justo antes de que se produzca ATP, por lo que la GAPDH podría ser usada como una diana de fármacos, de forma que si ésta se inhibe, A. vaginae consumirá ATP sin poder regenerarlo...
Atopobium vaginae is a Gram-positive anaerobic bacterium of the Coriobacteriaceae family that is held responsible for about 80% of diagnosed cases of bacterial vaginosis in humans along with Gardnerella vaginalis, a condition that can lead to obstetric complications, gynecological disorders and predisposition to opportunistic infections. Since the standard treatment (seven days, 800 mg of metronidazole per day) is not effective or long lasting, with relapses occurring in about 30% of cases within a month after treatment completion, new therapeutic approaches are a necessity.Because A. vaginae forms biofilms together with G. vaginalis, it has an anaerobic lifestyle and does not completely oxidize glucose, largely relying on glycolysis to obtain energy. During the first phase of the glycolytic pathway, the cell consumes two molecules of ATP for each molecule of glucose, while during the second phase it produces four molecules of ATP and two of NADH, thus creating a net balance of two molecules each of ATP of NADH. The enzyme D-glyceraldehyde-3-phosphate dehydrogenase (GAPDH) transforms glyceraldehyde-3-phosphate in 1,3-bisphosphoglycerate using NAD+ as cofactor, with the consumption of a molecule of inorganic phosphate and the generation of a molecule of NADH. This is the first reaction of the second phase of the glycolysis, right before producing ATP, so if GAPDH is inhibited with drugs, A. vaginae will consume ATP without regenerating it...
Atopobium vaginae is a Gram-positive anaerobic bacterium of the Coriobacteriaceae family that is held responsible for about 80% of diagnosed cases of bacterial vaginosis in humans along with Gardnerella vaginalis, a condition that can lead to obstetric complications, gynecological disorders and predisposition to opportunistic infections. Since the standard treatment (seven days, 800 mg of metronidazole per day) is not effective or long lasting, with relapses occurring in about 30% of cases within a month after treatment completion, new therapeutic approaches are a necessity.Because A. vaginae forms biofilms together with G. vaginalis, it has an anaerobic lifestyle and does not completely oxidize glucose, largely relying on glycolysis to obtain energy. During the first phase of the glycolytic pathway, the cell consumes two molecules of ATP for each molecule of glucose, while during the second phase it produces four molecules of ATP and two of NADH, thus creating a net balance of two molecules each of ATP of NADH. The enzyme D-glyceraldehyde-3-phosphate dehydrogenase (GAPDH) transforms glyceraldehyde-3-phosphate in 1,3-bisphosphoglycerate using NAD+ as cofactor, with the consumption of a molecule of inorganic phosphate and the generation of a molecule of NADH. This is the first reaction of the second phase of the glycolysis, right before producing ATP, so if GAPDH is inhibited with drugs, A. vaginae will consume ATP without regenerating it...
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Tesis inédita de la Universidad Complutense de Madrid, Facultad de Ciencias Biológicas, leída el 29 de Mayo de 2017