Towards designing a synthetic antituberculosis vaccine: The Rv3587c peptide inhibits mycobacterial entry to host cells

Mary Lilian Carabali-Isajar; Marisol Ocampo; Deisy Carolina Rodriguez; Magnolia Vanegas; Hernando Curtidor; Manuel Alfonso Patarroyo; Manuel Elkin Patarroyo

doi:10.1016/j.bmc.2018.03.044

Towards designing a synthetic antituberculosis vaccine: The Rv3587c peptide inhibits mycobacterial entry to host cells

Título traducido de la contribución: Hacia el diseño de una vacuna sintética contra la tuberculosis: El péptido Rv3587c inhibe la entrada de micobacterias a las células huéspedes

Mary Lilian Carabali-Isajar, Marisol Ocampo, Deisy Carolina Rodriguez, Magnolia Vanegas, Hernando Curtidor, Manuel Alfonso Patarroyo, Manuel Elkin Patarroyo

Producción científica: Contribución a una revista › Artículo › revisión exhaustiva

6 Citas (Scopus)

Resumen

La Mycobacterium tuberculosis está considerada como uno de los patógenos más exitosos en la historia de la humanidad, habiendo causado 1,7 millones de muertes en 2016. La cantidad de cepas resistentes y extensivamente resistentes ha aumentado; la BCG ha sido la única vacuna que se ha producido en más de 100 años, aunque todavía no es capaz de prevenir la forma más diseminada de la enfermedad en adultos: la tuberculosis pulmonar. Por lo tanto, la búsqueda de antígenos candidatos para una vacuna antituberculosa sigue en curso. Este trabajo reporta el uso de una metodología lógica y racional para encontrar tales antígenos, esta vez como péptidos derivados de la proteína de la membrana Rv3587c. Se utilizaron herramientas bioinformáticas para predecir la ubicación de la superficie de las micobacterias y la estructura de la proteína Rv3587c, mientras que se utilizó dicroísmo circular para determinar la estructura secundaria de los péptidos. Los ensayos de ligandos receptores identificaron 4 péptidos ligantes de alta actividad (HABPs) ligados específicamente a las células epiteliales alveolares A549 y a los macrófagos derivados de monocitos U937, cubriendo la región entre los aminoácidos 116 y 193. Se evaluó su capacidad para inhibir la invasión de H37Rv de la btt. En los HABPs capaces de evitar la entrada de micobacterias en las células huéspedes se observó el reconocimiento de anticuerpos de individuos que padecen tuberculosis activa y latente y de individuos sanos. Los resultados mostraron que 8 HABPs inhibieron dicha invasión, siendo dos de ellos comunes para ambas líneas celulares: 39265 (155VLAAYVYSLDNKRLWSNLDT173) y 39266 (174APSNETLVKTFSPGEQVTTY192). El péptido 39265 fue el menos reconocido por los anticuerpos de los sueros de los individuos evaluados en cada grupo. Según el modelo propuesto por la FIDIC para el desarrollo de vacunas sintéticas, el péptido 39265 se ha convertido en un antígeno candidato para una vacuna antituberculosa.

Título traducido de la contribución	Hacia el diseño de una vacuna sintética contra la tuberculosis: El péptido Rv3587c inhibe la entrada de micobacterias a las células huéspedes
Idioma original	Inglés estadounidense
Páginas (desde-hasta)	2401-2409
Número de páginas	9
Publicación	Bioorganic and Medicinal Chemistry
Volumen	26
N.º	9
DOI	https://doi.org/10.1016/j.bmc.2018.03.044
Estado	Publicada - may. 15 2018

Áreas temáticas de ASJC Scopus

Bioquímica
Medicina molecular
Biología molecular
Ciencias farmacéuticas
Descubrimiento de medicamentos
Bioquímica clínica
Química orgánica

ODS de las Naciones Unidas

Este resultado contribuye a los siguientes Objetivos de Desarrollo Sostenible

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10.1016/j.bmc.2018.03.044

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@article{331b99a0a7044a81bcba0bee3f959314,

title = "Towards designing a synthetic antituberculosis vaccine: The Rv3587c peptide inhibits mycobacterial entry to host cells",

abstract = "Mycobacterium tuberculosis is considered one of the most successful pathogens in the history of mankind, having caused 1.7 million deaths in 2016. The amount of resistant and extensively resistant strains has increased; BCG has been the only vaccine to be produced in more than 100 years though it is still unable to prevent the disease's most disseminated form in adults; pulmonary tuberculosis. The search is thus still on-going for candidate antigens for an antituberculosis vaccine. This paper reports the use of a logical and rational methodology for finding such antigens, this time as peptides derived from the Rv3587c membrane protein. Bioinformatics tools were used for predicting mycobacterial surface location and Rv3587c protein structure whilst circular dichroism was used for determining its peptides{\textquoteright} secondary structure. Receptor-ligand assays identified 4 high activity binding peptides (HABPs) binding specifically to A549 alveolar epithelial cells and U937 monocyte-derived macrophages, covering the region between amino acids 116 and 193. Their capability for inhibiting Mtb H37Rv invasion was evaluated. The recognition of antibodies from individuals suffering active and latent tuberculosis and from healthy individuals was observed in HABPs capable of avoiding mycobacterial entry to host cells. The results showed that 8 HABPs inhibited such invasion, two of them being common for both cell lines: 39265 (155VLAAYVYSLDNKRLWSNLDT173) and 39266 (174APSNETLVKTFSPGEQVTTY192). Peptide 39265 was the least recognised by antibodies from the individuals{\textquoteright} sera evaluated in each group. According to the model proposed by FIDIC regarding synthetic vaccine development, peptide 39265 has become a candidate antigen for an antituberculosis vaccine.",

author = "Carabali-Isajar, {Mary Lilian} and Marisol Ocampo and Rodriguez, {Deisy Carolina} and Magnolia Vanegas and Hernando Curtidor and Patarroyo, {Manuel Alfonso} and Patarroyo, {Manuel Elkin}",

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language = "English (US)",

volume = "26",

pages = "2401--2409",

journal = "Bioorganic and Medicinal Chemistry",

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Towards designing a synthetic antituberculosis vaccine: The Rv3587c peptide inhibits mycobacterial entry to host cells. / Carabali-Isajar, Mary Lilian; Ocampo, Marisol; Rodriguez, Deisy Carolina et al.
En: Bioorganic and Medicinal Chemistry, Vol. 26, N.º 9, 15.05.2018, p. 2401-2409.

Producción científica: Contribución a una revista › Artículo › revisión exhaustiva

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AU - Carabali-Isajar, Mary Lilian

AU - Ocampo, Marisol

AU - Rodriguez, Deisy Carolina

AU - Vanegas, Magnolia

AU - Curtidor, Hernando

AU - Patarroyo, Manuel Alfonso

AU - Patarroyo, Manuel Elkin

PY - 2018/5/15

Y1 - 2018/5/15

N2 - Mycobacterium tuberculosis is considered one of the most successful pathogens in the history of mankind, having caused 1.7 million deaths in 2016. The amount of resistant and extensively resistant strains has increased; BCG has been the only vaccine to be produced in more than 100 years though it is still unable to prevent the disease's most disseminated form in adults; pulmonary tuberculosis. The search is thus still on-going for candidate antigens for an antituberculosis vaccine. This paper reports the use of a logical and rational methodology for finding such antigens, this time as peptides derived from the Rv3587c membrane protein. Bioinformatics tools were used for predicting mycobacterial surface location and Rv3587c protein structure whilst circular dichroism was used for determining its peptides’ secondary structure. Receptor-ligand assays identified 4 high activity binding peptides (HABPs) binding specifically to A549 alveolar epithelial cells and U937 monocyte-derived macrophages, covering the region between amino acids 116 and 193. Their capability for inhibiting Mtb H37Rv invasion was evaluated. The recognition of antibodies from individuals suffering active and latent tuberculosis and from healthy individuals was observed in HABPs capable of avoiding mycobacterial entry to host cells. The results showed that 8 HABPs inhibited such invasion, two of them being common for both cell lines: 39265 (155VLAAYVYSLDNKRLWSNLDT173) and 39266 (174APSNETLVKTFSPGEQVTTY192). Peptide 39265 was the least recognised by antibodies from the individuals’ sera evaluated in each group. According to the model proposed by FIDIC regarding synthetic vaccine development, peptide 39265 has become a candidate antigen for an antituberculosis vaccine.

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Towards designing a synthetic antituberculosis vaccine: The Rv3587c peptide inhibits mycobacterial entry to host cells

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