The endothelin system has a significant role in the pathogenesis and progression of Mycobacterium tuberculosis infection
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2014
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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 bestcharacterized
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.
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CORREA, André F. et al. The endothelin system has a significant role in the pathogenesis and progression of Mycobacterium tuberculosis infection. Infection and Immunity, Washington, v. 82, n.12, p. 5154-5165, 2014.