title: Mycobacterium tuberculosisProlyl Oligopeptidase InducesIn vitroSecretion of Proinflammatory Cytokines by Peritoneal Macrophages.
abstract: Tuberculosis (TB) is a disease that leads to death over 1 million people per year worldwide and the biological mediators of this pathology are poorly established, preventing the implementation of effective therapies to improve outcomes in TB. Host-bacterium interaction is a key step to TB establishment and the proteases produced by these microorganisms seem to facilitate bacteria invasion, migration and host immune response evasion. We presented, for the first time, the identification, biochemical characterization, molecular dynamics (MDs) and immunomodulatory properties of a prolyl oligopeptidase (POP) fromMycobacterium tuberculosis(POPMt). POP is a serine protease that hydrolyzes substrates with high specificity for proline residues and has already been characterized as virulence factor in infectious diseases. POPMt reveals catalytic activity upon N-Suc-Gly-Pro-Leu-Gly-Pro-AMC, a recognized POP substrate, with optimal activity at pH 7.5 and 37°C. The enzyme presents KMand Kcat/KMvalues of 108 μM and 21.838 mM-1s-1, respectively. MDs showed that POPMt structure is similar to that of others POPs, which consists of a cylindrical architecture divided into an α/β hydrolase catalytic domain and a β-propeller domain. Finally, POPMt was capable of triggeringin vitrosecretion of proinflammatory cytokines by peritoneal macrophages, an event dependent on POPMt intact structure. Our data suggests that POPMt may contribute to an inflammatory response duringM. tuberculosisinfection.
authors.affiliation: Pathogen-Host Interface Laboratory, Department of Cell Biology, The University of Brasília, Brasília Brazil.
authors.forename: Brina
authors.initials: B
authors.lastname: Portugal
authors.affiliation: Pathogen-Host Interface Laboratory, Department of Cell Biology, The University of Brasília, BrasíliaBrazil; Instituto de Patologia Tropical e Saúde Pública, Universidade Federal de GoiásGoiânia, Brazil.
authors.forename: Flávia N
authors.initials: FN
authors.lastname: Motta
authors.affiliation: Pathogen-Host Interface Laboratory, Department of Cell Biology, The University of Brasília, BrasíliaBrazil; Instituto de Patologia Tropical e Saúde Pública, Universidade Federal de GoiásGoiânia, Brazil.
authors.forename: Andre F
authors.initials: AF
authors.lastname: Correa
authors.affiliation: Physics Course and Postgraduate Program in Genomic Sciences and Biotechnology, Catholic University of Brasília Brasília, Brazil.
authors.forename: Diego O
authors.initials: DO
authors.lastname: Nolasco
authors.affiliation: Pathogen-Host Interface Laboratory, Department of Cell Biology, The University of Brasília, Brasília Brazil.
authors.forename: Hugo
authors.initials: H
authors.lastname: de Almeida
authors.affiliation: Laboratory of Immunology and Inflammation, Department of Cell Biology, The University of Brasília Brasília, Brazil.
authors.forename: Kelly G
authors.initials: KG
authors.lastname: Magalhães
authors.affiliation: Laboratório Central de Saúde Pública do Distrito Federal Brasília, Brazil.
authors.forename: Ana L V
authors.initials: AL
authors.lastname: Atta
authors.affiliation: Laboratório Central de Saúde Pública do Distrito Federal Brasília, Brazil.
authors.forename: Francisco D
authors.initials: FD
authors.lastname: Vieira
authors.affiliation: Pathogen-Host Interface Laboratory, Department of Cell Biology, The University of Brasília, Brasília Brazil.
authors.forename: Izabela M D
authors.initials: IM
authors.lastname: Bastos
authors.affiliation: Pathogen-Host Interface Laboratory, Department of Cell Biology, The University of Brasília, Brasília Brazil.
authors.forename: Jaime M
authors.initials: JM
authors.lastname: Santana
keywords: Mycobacterium tuberculosis protease; fluorescence spectroscopy; molecular dynamic; proinflammatory cytokines; prolyl oligopeptidase; serine protease; tuberculosis