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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....
Autores principales: | , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
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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. |
format | Online Article Text |
id | pubmed-7697726 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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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