Pelaez Coyotl 2020 Pharmaceutics
|Peláez Coyotl EA, Barrios Palacios J, Muciño G, Moreno-Blas D, Costas M, Montiel Montes T, Diener C, Uribe-Carvajal S, Massieu L, Castro-Obregón S, Espinosa OR, Mata Espinosa D, Barrios-Payan J, León Contreras JC, Corzo G, Hernández-Pando R, Del Rio G (2020) Antimicrobial peptide against Mycobacterium tuberculosis that activates autophagy is an effective treatment for tuberculosis. Pharmaceutics 12:E1071.|
Pelaez Coyotl Erika A, Barrios Palacios Jacqueline, Mucino Gabriel, Moreno-Blas Daniel, Costas Miguel, Montiel Montes Teresa, Diener Christian, Uribe-Carvajal Salvador, Massieu Lourdes, Castro-Obregon Susana, Espinosa Octavio Ramos, Mata Espinosa Dulce, Barrios-Payan Jorge, Contreras Juan Carlos Leon, Corzo Gerardo, Hernandez-Pando Rogelio, Del Rio Gabriel (2020) Pharmaceutics
Abstract: 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.
Labels: MiParea: Respiration, Pharmacology;toxicology Pathology: Infectious
Organism: Mouse Tissue;cell: Fibroblast Preparation: Intact cells
Coupling state: ROUTINE, ET