Antimicrobial Peptide against <i>Mycobacterium Tuberculosis</i> That Activates Autophagy Is an Effective Treatment for Tuberculosis
<i>Mycobacterium tuberculosis</i> (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-ho...
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-11-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/12/11/1071 |
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| author | Erika A. Peláez Coyotl Jacqueline Barrios Palacios Gabriel Muciño Daniel Moreno-Blas Miguel Costas Teresa Montiel Montes Christian Diener Salvador Uribe-Carvajal Lourdes Massieu Susana Castro-Obregón Octavio Ramos Espinosa Dulce Mata Espinosa Jorge Barrios-Payan Juan Carlos León Contreras Gerardo Corzo Rogelio Hernández-Pando Gabriel Del Rio |
| author_facet | Erika A. Peláez Coyotl Jacqueline Barrios Palacios Gabriel Muciño Daniel Moreno-Blas Miguel Costas Teresa Montiel Montes Christian Diener Salvador Uribe-Carvajal Lourdes Massieu Susana Castro-Obregón Octavio Ramos Espinosa Dulce Mata Espinosa Jorge Barrios-Payan Juan Carlos León Contreras Gerardo Corzo Rogelio Hernández-Pando Gabriel Del Rio |
| author_sort | Erika A. Peláez Coyotl |
| collection | DOAJ |
| description | <i>Mycobacterium tuberculosis</i> (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. |
| first_indexed | 2024-03-10T14:58:37Z |
| format | Article |
| id | doaj.art-301557ccf09347ec99a2a4e8bd2463b4 |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-10T14:58:37Z |
| publishDate | 2020-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-301557ccf09347ec99a2a4e8bd2463b42023-11-20T20:20:34ZengMDPI AGPharmaceutics1999-49232020-11-011211107110.3390/pharmaceutics12111071Antimicrobial Peptide against <i>Mycobacterium Tuberculosis</i> That Activates Autophagy Is an Effective Treatment for TuberculosisErika A. Peláez Coyotl0Jacqueline Barrios Palacios1Gabriel Muciño2Daniel Moreno-Blas3Miguel Costas4Teresa Montiel Montes5Christian Diener6Salvador Uribe-Carvajal7Lourdes Massieu8Susana Castro-Obregón9Octavio Ramos Espinosa10Dulce Mata Espinosa11Jorge Barrios-Payan12Juan Carlos León Contreras13Gerardo Corzo14Rogelio Hernández-Pando15Gabriel Del Rio16Department of Biochemistry and Structural Biology, Institute of Cellular Physiology, National Autonomous University of Mexico (UNAM), 04510 Mexico City, MexicoExperimental Pathology Section, National Institute of Medical Sciences and Nutrition Salvador Zubirán, 14080 Mexico City, MexicoDepartment of Neurodevelopment and Physiology, Instituto de Fisiologia Celular, National Autonomous University of Mexico, 04510 Mexico City, MexicoDepartment of Neurodevelopment and Physiology, Instituto de Fisiologia Celular, National Autonomous University of Mexico, 04510 Mexico City, MexicoLaboratorio de Biofisicoquímica, Departamento de Fisicoquímica, Facultad de Química, Universidad Nacional Autonoma de Mexico, 04510 Mexico City, MexicoDepartment of Molecular Neuropathology, Institute of Cellular Physiology, National Autonomous University of Mexico (UNAM), 04510 Mexico City, MexicoDepartment of Biochemistry and Structural Biology, Institute of Cellular Physiology, National Autonomous University of Mexico (UNAM), 04510 Mexico City, MexicoDepartment of Molecular Genetics, Institute of Cellular Physiology, National Autonomous University of Mexico, 04510 Mexico City, MexicoDepartment of Molecular Neuropathology, Institute of Cellular Physiology, National Autonomous University of Mexico (UNAM), 04510 Mexico City, MexicoDepartment of Neurodevelopment and Physiology, Instituto de Fisiologia Celular, National Autonomous University of Mexico, 04510 Mexico City, MexicoExperimental Pathology Section, National Institute of Medical Sciences and Nutrition Salvador Zubirán, 14080 Mexico City, MexicoExperimental Pathology Section, National Institute of Medical Sciences and Nutrition Salvador Zubirán, 14080 Mexico City, MexicoExperimental Pathology Section, National Institute of Medical Sciences and Nutrition Salvador Zubirán, 14080 Mexico City, MexicoExperimental Pathology Section, National Institute of Medical Sciences and Nutrition Salvador Zubirán, 14080 Mexico City, MexicoDepartment of Molecular Medicine and Bioprocesses, Institute of Biotechnology, National Autonomous University of Mexico (UNAM), 62210 Cuernavaca Morelos, MexicoExperimental Pathology Section, National Institute of Medical Sciences and Nutrition Salvador Zubirán, 14080 Mexico City, MexicoDepartment of Biochemistry and Structural Biology, Institute of Cellular Physiology, National Autonomous University of Mexico (UNAM), 04510 Mexico City, Mexico<i>Mycobacterium tuberculosis</i> (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.https://www.mdpi.com/1999-4923/12/11/1071antimicrobial peptidetuberculosisautophagyiztli peptidemultidrug resistant |
| spellingShingle | Erika A. Peláez Coyotl Jacqueline Barrios Palacios Gabriel Muciño Daniel Moreno-Blas Miguel Costas Teresa Montiel Montes Christian Diener Salvador Uribe-Carvajal Lourdes Massieu Susana Castro-Obregón Octavio Ramos Espinosa Dulce Mata Espinosa Jorge Barrios-Payan Juan Carlos León Contreras Gerardo Corzo Rogelio Hernández-Pando Gabriel Del Rio Antimicrobial Peptide against <i>Mycobacterium Tuberculosis</i> That Activates Autophagy Is an Effective Treatment for Tuberculosis Pharmaceutics antimicrobial peptide tuberculosis autophagy iztli peptide multidrug resistant |
| title | Antimicrobial Peptide against <i>Mycobacterium Tuberculosis</i> That Activates Autophagy Is an Effective Treatment for Tuberculosis |
| title_full | Antimicrobial Peptide against <i>Mycobacterium Tuberculosis</i> That Activates Autophagy Is an Effective Treatment for Tuberculosis |
| title_fullStr | Antimicrobial Peptide against <i>Mycobacterium Tuberculosis</i> That Activates Autophagy Is an Effective Treatment for Tuberculosis |
| title_full_unstemmed | Antimicrobial Peptide against <i>Mycobacterium Tuberculosis</i> That Activates Autophagy Is an Effective Treatment for Tuberculosis |
| title_short | Antimicrobial Peptide against <i>Mycobacterium Tuberculosis</i> That Activates Autophagy Is an Effective Treatment for Tuberculosis |
| title_sort | antimicrobial peptide against i mycobacterium tuberculosis i that activates autophagy is an effective treatment for tuberculosis |
| topic | antimicrobial peptide tuberculosis autophagy iztli peptide multidrug resistant |
| url | https://www.mdpi.com/1999-4923/12/11/1071 |
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