Título:	The activity of a Hexameric M17 Metallo-Aminopeptidase is associated with survival of Mycobacterium tuberculosis
Autor(es):	Corrêa, André França Bastos, Izabela Marques Dourado Neves, David Kipnis, André Kipnis, Ana Paula Junqueira Santana, Jaime Martins de
Assunto:	Tuberculose Medicamentos Proteases
Data de publicação:	27-Mar-2017
Editora:	Frontiers
Referência:	CORREA, Andre F. et al. The activity of a Hexameric M17 Metallo-Aminopeptidase is associated with survival of Mycobacterium tuberculosis. Frontiers in Microbiology, v. 8, Article 204, 27 mar. 2017. Disponível em: <http://journal.frontiersin.org/article/10.3389/fmicb.2017.00504/full>. Acesso em: 21 jun. 2017. doi: http://journal.frontiersin.org/article/10.3389/fmicb.2017.00504/full.
Abstract:	Mycobacterium tuberculosis is one of the most prevalent human pathogens causing millions of deaths in the last years. Moreover, tuberculosis (TB) treatment has become increasingly challenging owing to the emergence of multidrug resistant M. tuberculosis strains. Thus, there is an immediate need for the development of new anti-TB drugs. Proteases appear to be a promising approach and may lead to shortened and effective treatments for drug-resistant TB. Although the M. tuberculosis genome predicts more than 100 genes encoding proteases, only a few of them have been studied. Aminopeptidases constitute a set of proteases that selectively remove amino acids from the N-terminus of proteins and peptides and may act as virulence factors, essential for survival and maintenance of many microbial pathogens. Here, we characterized a leucine aminopeptidase of M. tuberculosis (MtLAP) as a cytosolic oligomeric metalloaminopeptidase. Molecular and enzymatic properties lead us to classify MtLAP as a typical member of the peptidase family M17. Furthermore, the aminopeptidase inhibitor bestatin strongly inhibited MtLAP activity, in vitro M. tuberculosis growth and macrophage infection. In murine model of TB, bestatin treatment reduced bacterial burden and lesion in the lungs of infected mice. Thus, our data suggest that MtLAP participates in important metabolic pathways of M. tuberculosis necessary for its survival and virulence and consequently may be a promising target for new anti-TB drugs.
Licença:	Copyright © 2017 Correa, Bastos, Neves, Kipnis, Junqueira-Kipnis and de Santana. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
DOI:	https://dx.doi.org/10.3389/fmicb.2017.00504
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