Diseño, síntesis, caracterización y evaluación in vitro de la actividad de los péptidos antimicrobianos contra bacterias patógenas resistentes a antibióticos
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Palabras clave

Antimicrobial peptides; microbial resistance; antimicrobial activity. péptidos antimicrobianos; resistencia microbiana; actividad antimicrobiana.

Cómo citar

Ortiz López, C. (2019). Diseño, síntesis, caracterización y evaluación in vitro de la actividad de los péptidos antimicrobianos contra bacterias patógenas resistentes a antibióticos. Rev. Acad. Colomb. Cienc. Ex. Fis. Nat., 43(169), 614-627. https://doi.org/10.18257/raccefyn.864

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Resumen

Los péptidos antimicrobianos han atraído mucha atención como nuevos agentes terapéuticos contra enfermedades infecciosas. En este estudio se hizo el diseño racional in silico de 18 péptidos catiónicos con actividad antimicrobiana contra bacterias patógenas resistentes utilizando el programa DEPRAMP desarrollado en el Grupo de Investigación en Bioquímica y Microbiología de la Universidad Industrial de Santander. Posteriormente, los péptidos diseñados se sintetizaron en fase sólida con el método de 9-fluorenilmetoxicarbonilo en medio ácido. Se obtuvieron secuencias cortas de 17 aminoácidos con un grado de pureza entre 95 y 98 %, estructura secundaria de hélice alfa, carga neta catiónica (entre +3 y +6), punto isoeléctrico entre 10,04 y 12,03 e índice de hidropatía entre -0,62 y 1,14. Todos los péptidos antimicrobianos mostraron actividad antibacteriana y bactericida in vitro frente al menos una de las cepas patógenas estudiadas: Escherichia coli O157: H7, Pseudomonas aeruginosa y Staphylococcus aureus resistente a la meticilina. Los péptidos antimicrobianos GIBIM-P5S9K y GIBIM-P5F8W registraron la mejor actividad antibacteriana, alcanzando una concentración mínima inhibitoria (CMI 99) en rangos de 0,5 a 25 μM frente a las tres cepas evaluadas, de las cuales Escherichia coli O157: H7 fue la más sensible frente al péptido antimicrobiano GIBIMP5F8W, con una CMI 99 de 0,5 μM y una concentración mínima bactericida de 10 μM, en tanto que la cepa de Pseudomonas aeruginosa fue la más resistente, con una CMI de más de 100 μM frente a más de cinco péptidos antimicrobianos. La toxicidad de los péptidos sobre los eritrocitos produjo un porcentaje de hemólisis menor al 40 % en concentraciones de 50 μM. Por su parte, en las líneas celulares de carcinoma de pulmón A549 y HepG2, el único compuesto que presentó toxicidad fue GIBIM-P5F8W, presentando un 36% de células viables en concentraciones de 100 μM del péptido en la línea celular A549.

https://doi.org/10.18257/raccefyn.864
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