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SHR Neuro Cancer Cardio Lipid Metab Microb

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.
Antimicrobial Peptide against Mycobacterium Tuberculosis That Activates Autophagy Is an Effective Treatment for Tuberculosis.
Pharmaceutics. 2020; 12(11): Doi: 10.3390/pharmaceutics12111071 [OPEN ACCESS]
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Co-authors Med Uni Graz: Diener Christian
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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.
Find related publications in this database (Keywords): antimicrobial peptide; tuberculosis; autophagy; iztli peptide; multidrug resistant