title: The endothelin system has a significant role in the pathogenesis and progression of Mycobacterium tuberculosis infection.
abstract: Tuberculosis (TB) remains a major global health problem, and although multiple studies have addressed the relationship between Mycobacterium tuberculosis and the host on an immunological level, few studies have addressed the impact of host physiological responses. Proteases produced by bacteria have been associated with important alterations in the host tissues, and a limited number of these enzymes have been characterized in mycobacterial species. M. tuberculosis produces a protease called Zmp1, which appears to be associated with virulence and has a putative action as an endothelin-converting enzyme. Endothelins are a family of vasoactive peptides, of which 3 distinct isoforms exist, and endothelin 1 (ET-1) is the most abundant and the best-characterized isoform. The aim of this work was to characterize the Zmp1 protease and evaluate its role in pathogenicity. Here, we have shown that M. tuberculosis produces and secretes an enzyme with ET-1 cleavage activity. These data demonstrate a possible role of Zmp1 for mycobacterium-host interactions and highlights its potential as a drug target. Moreover, the results suggest that endothelin pathways have a role in the pathogenesis of M. tuberculosis infections, and ETA or ETB receptor signaling can modulate the host response to the infection. We hypothesize that a balance between Zmp1 control of ET-1 levels and ETA/ETB signaling can allow M. tuberculosis adaptation and survival in the lung tissues.
authors.affiliation: Laboratório de Interação Parasito-Hospedeiro, Instituto de Biologia, Universidade de Brasília, Brasília, Brazil Instituto de Patologia Tropical e Saúde Pública, Universidade Federal de Goiás, Goiânia, Brazil.
authors.forename: Andre F
authors.initials: AF
authors.lastname: Correa
authors.affiliation: Laboratório de Biologia Molecular, Instituto de Ciências Biológicas, Universidade Federal de Goiás, Goiânia, Brazil.
authors.forename: Alexandre M
authors.initials: AM
authors.lastname: Bailão
authors.affiliation: Laboratório de Interação Parasito-Hospedeiro, Instituto de Biologia, Universidade de Brasília, Brasília, Brazil.
authors.forename: Izabela M D
authors.initials: IM
authors.lastname: Bastos
authors.affiliation: Colorado State University, Fort Collins, Colorado, USA.
authors.forename: Ian M
authors.initials: IM
authors.lastname: Orme
authors.affiliation: Laboratório de Biologia Molecular, Instituto de Ciências Biológicas, Universidade Federal de Goiás, Goiânia, Brazil.
authors.forename: Célia M A
authors.initials: CM
authors.lastname: Soares
authors.affiliation: Instituto de Patologia Tropical e Saúde Pública, Universidade Federal de Goiás, Goiânia, Brazil.
authors.forename: Andre
authors.initials: A
authors.lastname: Kipnis
authors.affiliation: Laboratório de Interação Parasito-Hospedeiro, Instituto de Biologia, Universidade de Brasília, Brasília, Brazil jsantana@unb.br apkipnis@gmail.com.
authors.forename: Jaime M
authors.initials: JM
authors.lastname: Santana
authors.affiliation: Instituto de Patologia Tropical e Saúde Pública, Universidade Federal de Goiás, Goiânia, Brazil jsantana@unb.br apkipnis@gmail.com.
authors.forename: Ana Paula
authors.initials: AP
authors.lastname: Junqueira-Kipnis
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000378:metabolism*; D004195:Disease Models, Animal; D019332:Endothelin-1 / Q000378:metabolism*; D005260:Female; D054884:Host-Pathogen Interactions; D045726:Metalloproteases / Q000378:metabolism*; D008810:Mice, Inbred C57BL; D009169:Mycobacterium tuberculosis / Q000201:enzymology / Q000502:physiology*; D059748:Proteolysis; D014376:Tuberculosis / Q000382:microbiology*; D037521:Virulence Factors / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D019332:Endothelin-1; D037521:Virulence Factors; D045726:Metalloproteases; C568073:Zmp1 protein, Mycobacterium tuberculosis