Mycobacterium tuberculosis H37Rv LpqG Protein Peptides Can Inhibit Mycobacterial Entry through Specific Interactions

Christian David Sánchez-Barinas; Marisol Ocampo; Magnolia Vanegas; Jeimmy Johana Castañeda-Ramirez; Manuel Alfonso Patarroyo; Manuel Elkin Patarroyo

doi:10.3390/molecules23030526

Mycobacterium tuberculosis H37Rv LpqG Protein Peptides Can Inhibit Mycobacterial Entry through Specific Interactions

Título traducido de la contribución: Los péptidos de la proteína Mycobacterium tuberculosis H37Rv LpqG pueden inhibir la entrada de micobacterias a través de interacciones específicas.

Christian David Sánchez-Barinas, Marisol Ocampo, Magnolia Vanegas, Jeimmy Johana Castañeda-Ramirez, Manuel Alfonso Patarroyo, Manuel Elkin Patarroyo

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

5 Citas (Scopus)

Resumen

La Mycobacterium tuberculosis es el agente causal de la tuberculosis, una enfermedad que causa gran mortalidad en todo el mundo. Como parte de una metodología sistemática para estudiar las proteínas de superficie de M. tuberculosis que podrían estar involucradas en las interacciones huésped-patógeno, nuestro grupo encontró que la proteína de superficie LpqG (Rv3623) encontrada en las cepas del complejo M. tuberculosis estaba localizada en la envoltura micobacteriana y que el péptido 16661 (21SGCDSHNSGSLGSLGADPRQVTVY40) tenía una alta unión específica con los macrófagos derivados de los monocitos U937 e inhibía la entrada de micobacterias a dichas células de una manera dependiente de la concentración. Se encontró una región con alta unión específica a las células epiteliales alveolares A549 que tenía una baja inhibición de entrada de micobacterias. Como se sugirió en estudios anteriores, las secuencias relevantes en la interacción huésped-patógeno no inducen una respuesta inmune y los péptidos caracterizados como HABP son mal reconocidos por los sueros de los individuos, independientemente de si han estado en contacto con M. tuberculosis. Nuestro enfoque para diseñar una vacuna antituberculosa sintética multiepitópica se ha basado en la identificación de secuencias involucradas en la interacción entre las células objetivo y las micobacterias de diferentes proteínas y en la modificación de su secuencia para mejorar sus características inmunogénicas, lo que significa que la secuencia del péptido 16661 debe ser considerada en dicho diseño.

Título traducido de la contribución	Los péptidos de la proteína Mycobacterium tuberculosis H37Rv LpqG pueden inhibir la entrada de micobacterias a través de interacciones específicas.
Idioma original	Inglés estadounidense
Número de artículo	526
Publicación	Molecules
Volumen	23
N.º	3
DOI	https://doi.org/10.3390/molecules23030526
Estado	Publicada - ene. 1 2018

Áreas temáticas de ASJC Scopus

Química analítica
Química (miscelánea)
Medicina molecular
Ciencias farmacéuticas
Descubrimiento de medicamentos
Química física y teórica
Química orgánica

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title = "Mycobacterium tuberculosis H37Rv LpqG Protein Peptides Can Inhibit Mycobacterial Entry through Specific Interactions",

abstract = "Mycobacterium tuberculosis is the causative agent of tuberculosis, a disease causing major mortality worldwide. As part of a systematic methodology for studying M. tuberculosis surface proteins which might be involved in host-pathogen interactions, our group found that LpqG surface protein (Rv3623) found in M. tuberculosis complex strains was located on the mycobacterial envelope and that peptide 16661 (21SGCDSHNSGSLGADPRQVTVY40) had high specific binding to U937 monocyte-derived macrophages and inhibited mycobacterial entry to such cells in a concentration-dependent way. A region having high specific binding to A549 alveolar epithelial cells was found which had low mycobacterial entry inhibition. As suggested in previous studies, relevant sequences in the host-pathogen interaction do not induce an immune response and peptides characterised as HABPs are poorly recognised by sera from individuals regardless of whether they have been in contact with M. tuberculosis. Our approach to designing a synthetic, multi-epitope anti-tuberculosis vaccine has been based on identifying sequences involved in different proteins' mycobacteria-target cell interaction and modifying their sequence to improve their immunogenic characteristics, meaning that peptide 16661 sequence should be considered in such design.",

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AU - Patarroyo, Manuel Alfonso

AU - Patarroyo, Manuel Elkin

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AB - Mycobacterium tuberculosis is the causative agent of tuberculosis, a disease causing major mortality worldwide. As part of a systematic methodology for studying M. tuberculosis surface proteins which might be involved in host-pathogen interactions, our group found that LpqG surface protein (Rv3623) found in M. tuberculosis complex strains was located on the mycobacterial envelope and that peptide 16661 (21SGCDSHNSGSLGADPRQVTVY40) had high specific binding to U937 monocyte-derived macrophages and inhibited mycobacterial entry to such cells in a concentration-dependent way. A region having high specific binding to A549 alveolar epithelial cells was found which had low mycobacterial entry inhibition. As suggested in previous studies, relevant sequences in the host-pathogen interaction do not induce an immune response and peptides characterised as HABPs are poorly recognised by sera from individuals regardless of whether they have been in contact with M. tuberculosis. Our approach to designing a synthetic, multi-epitope anti-tuberculosis vaccine has been based on identifying sequences involved in different proteins' mycobacteria-target cell interaction and modifying their sequence to improve their immunogenic characteristics, meaning that peptide 16661 sequence should be considered in such design.

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Mycobacterium tuberculosis H37Rv LpqG Protein Peptides Can Inhibit Mycobacterial Entry through Specific Interactions

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