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Antimicrobial Peptide against Mycobacterium Tuberculosis That Activates Autophagy Is an Effective Treatment for Tuberculosis

Mycobacterium tuberculosis (MTB) is the principal cause of human tuberculosis (TB), which is a serious health problem worldwide. The development of innovative therapeutic modalities to treat TB is mainly due to the emergence of multi drug resistant (MDR) TB. Autophagy is a cell-host defense process....

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Autores principales: Peláez Coyotl, Erika A., Barrios Palacios, Jacqueline, Muciño, Gabriel, Moreno-Blas, Daniel, Costas, Miguel, Montiel Montes, Teresa, Diener, Christian, Uribe-Carvajal, Salvador, Massieu, Lourdes, Castro-Obregón, Susana, Espinosa, Octavio Ramos, Mata Espinosa, Dulce, Barrios-Payan, Jorge, León Contreras, Juan Carlos, Corzo, Gerardo, Hernández-Pando, Rogelio, Del Rio, Gabriel
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7697726/
https://www.ncbi.nlm.nih.gov/pubmed/33182483
http://dx.doi.org/10.3390/pharmaceutics12111071
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author Peláez Coyotl, Erika A.
Barrios Palacios, Jacqueline
Muciño, Gabriel
Moreno-Blas, Daniel
Costas, Miguel
Montiel Montes, Teresa
Diener, Christian
Uribe-Carvajal, Salvador
Massieu, Lourdes
Castro-Obregón, Susana
Espinosa, Octavio Ramos
Mata Espinosa, Dulce
Barrios-Payan, Jorge
León Contreras, Juan Carlos
Corzo, Gerardo
Hernández-Pando, Rogelio
Del Rio, Gabriel
author_facet Peláez Coyotl, Erika A.
Barrios Palacios, Jacqueline
Muciño, Gabriel
Moreno-Blas, Daniel
Costas, Miguel
Montiel Montes, Teresa
Diener, Christian
Uribe-Carvajal, Salvador
Massieu, Lourdes
Castro-Obregón, Susana
Espinosa, Octavio Ramos
Mata Espinosa, Dulce
Barrios-Payan, Jorge
León Contreras, Juan Carlos
Corzo, Gerardo
Hernández-Pando, Rogelio
Del Rio, Gabriel
author_sort Peláez Coyotl, Erika A.
collection PubMed
description Mycobacterium tuberculosis (MTB) is the principal cause of human tuberculosis (TB), which is a serious health problem worldwide. The development of innovative therapeutic modalities to treat TB is mainly due to the emergence of multi drug resistant (MDR) TB. Autophagy is a cell-host defense process. Previous studies have reported that autophagy-activating agents eliminate intracellular MDR MTB. Thus, combining a direct antibiotic activity against circulating bacteria with autophagy activation to eliminate bacteria residing inside cells could treat MDR TB. We show that the synthetic peptide, IP-1 (KFLNRFWHWLQLKPGQPMY), induced autophagy in HEK293T cells and macrophages at a low dose (10 μM), while increasing the dose (50 μM) induced cell death; IP-1 induced the secretion of TNFα in macrophages and killed Mtb at a dose where macrophages are not killed by IP-1. Moreover, IP-1 showed significant therapeutic activity in a mice model of progressive pulmonary TB. In terms of the mechanism of action, IP-1 sequesters ATP in vitro and inside living cells. Thus, IP-1 is the first antimicrobial peptide that eliminates MDR MTB infection by combining four activities: reducing ATP levels, bactericidal activity, autophagy activation, and TNFα secretion.
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spelling pubmed-76977262020-11-29 Antimicrobial Peptide against Mycobacterium Tuberculosis That Activates Autophagy Is an Effective Treatment for Tuberculosis Peláez Coyotl, Erika A. Barrios Palacios, Jacqueline Muciño, Gabriel Moreno-Blas, Daniel Costas, Miguel Montiel Montes, Teresa Diener, Christian Uribe-Carvajal, Salvador Massieu, Lourdes Castro-Obregón, Susana Espinosa, Octavio Ramos Mata Espinosa, Dulce Barrios-Payan, Jorge León Contreras, Juan Carlos Corzo, Gerardo Hernández-Pando, Rogelio Del Rio, Gabriel Pharmaceutics Article Mycobacterium tuberculosis (MTB) is the principal cause of human tuberculosis (TB), which is a serious health problem worldwide. The development of innovative therapeutic modalities to treat TB is mainly due to the emergence of multi drug resistant (MDR) TB. Autophagy is a cell-host defense process. Previous studies have reported that autophagy-activating agents eliminate intracellular MDR MTB. Thus, combining a direct antibiotic activity against circulating bacteria with autophagy activation to eliminate bacteria residing inside cells could treat MDR TB. We show that the synthetic peptide, IP-1 (KFLNRFWHWLQLKPGQPMY), induced autophagy in HEK293T cells and macrophages at a low dose (10 μM), while increasing the dose (50 μM) induced cell death; IP-1 induced the secretion of TNFα in macrophages and killed Mtb at a dose where macrophages are not killed by IP-1. Moreover, IP-1 showed significant therapeutic activity in a mice model of progressive pulmonary TB. In terms of the mechanism of action, IP-1 sequesters ATP in vitro and inside living cells. Thus, IP-1 is the first antimicrobial peptide that eliminates MDR MTB infection by combining four activities: reducing ATP levels, bactericidal activity, autophagy activation, and TNFα secretion. MDPI 2020-11-09 /pmc/articles/PMC7697726/ /pubmed/33182483 http://dx.doi.org/10.3390/pharmaceutics12111071 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Peláez Coyotl, Erika A.
Barrios Palacios, Jacqueline
Muciño, Gabriel
Moreno-Blas, Daniel
Costas, Miguel
Montiel Montes, Teresa
Diener, Christian
Uribe-Carvajal, Salvador
Massieu, Lourdes
Castro-Obregón, Susana
Espinosa, Octavio Ramos
Mata Espinosa, Dulce
Barrios-Payan, Jorge
León Contreras, Juan Carlos
Corzo, Gerardo
Hernández-Pando, Rogelio
Del Rio, Gabriel
Antimicrobial Peptide against Mycobacterium Tuberculosis That Activates Autophagy Is an Effective Treatment for Tuberculosis
title Antimicrobial Peptide against Mycobacterium Tuberculosis That Activates Autophagy Is an Effective Treatment for Tuberculosis
title_full Antimicrobial Peptide against Mycobacterium Tuberculosis That Activates Autophagy Is an Effective Treatment for Tuberculosis
title_fullStr Antimicrobial Peptide against Mycobacterium Tuberculosis That Activates Autophagy Is an Effective Treatment for Tuberculosis
title_full_unstemmed Antimicrobial Peptide against Mycobacterium Tuberculosis That Activates Autophagy Is an Effective Treatment for Tuberculosis
title_short Antimicrobial Peptide against Mycobacterium Tuberculosis That Activates Autophagy Is an Effective Treatment for Tuberculosis
title_sort antimicrobial peptide against mycobacterium tuberculosis that activates autophagy is an effective treatment for tuberculosis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7697726/
https://www.ncbi.nlm.nih.gov/pubmed/33182483
http://dx.doi.org/10.3390/pharmaceutics12111071
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