The activity of a hexameric m17 metallo-aminopeptidase is associated with survival of mycobacterium tuberculosis
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2017
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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 metallo aminopeptidase. 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.
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MtLAP, Proteases, Tuberculosis, leucine aminopeptidase, M17 metallo protease, Bestatin
Citação
CORREA, Andre F.; BASTOS, Izabela M. D.; NEVES, David; KIPINS, André; JUNQUEIRA-KIPNIS, Ana P.; SANTANA, Jaime M. The activity of a hexameric m17 metallo-aminopeptidase is associated with survival of mycobacterium tuberculosis. Frontiers in Microbiology , Lausanne, v. 8, p. 504-517, 2017. DOI: 10.3389/fmicb.2017.00504. Disponível em: .https://pubmed.ncbi.nlm.nih.gov/28396657/ Acesso em: 20 ago. 2024.