Expression of recombinant protease MarP from Mycobacterium tuberculosis in Pichia pastoris and its effect on human monocytes

García-González, Gerardo; Ascacio-Martínez, Jorge A.; Hernández-Bello, Romel; González, Gloria M.; Palma-Nicolás, José Prisco

doi:10.1007/s10529-021-03149-3

Cited by 5 publications

(2 citation statements)

References 16 publications

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“…Additionally, Rv3671c confers protection to M . tb against acid stress and enhances its ability to withstand phagosome–lysosome fusion [ 42 ]. It has been shown that inactivation of HtrA-like serine protease pepD alters the virulence of M .…”

Section: Discussionmentioning

confidence: 99%

“…The M.tb serine protease Rv3194c has been linked to M.tb pathogenicity, given that it hinders phagocytosis and chemotaxis, thereby promoting M.tb persistence in the lungs [41]. Additionally, Rv3671c confers protection to M.tb against acid stress and enhances its ability to withstand phagosome-lysosome fusion [42]. It has been shown that inactivation of HtrA-like serine protease pepD alters the virulence of M.tb in a mouse model [43].…”

Section: Plos Pathogensmentioning

confidence: 99%

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Serine protease Rv2569c facilitates transmission of Mycobacterium tuberculosis via disrupting the epithelial barrier by cleaving E-cadherin

Zang,

Zhang,

Jiang

et al. 2024

PLoS Pathog

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Epithelial cells function as the primary line of defense against invading pathogens. However, bacterial pathogens possess the ability to compromise this barrier and facilitate the transmigration of bacteria. Nonetheless, the specific molecular mechanism employed by Mycobacterium tuberculosis (M.tb) in this process is not fully understood. Here, we investigated the role of Rv2569c in M.tb translocation by assessing its ability to cleave E-cadherin, a crucial component of cell-cell adhesion junctions that are disrupted during bacterial invasion. By utilizing recombinant Rv2569c expressed in Escherichia coli and subsequently purified through affinity chromatography, we demonstrated that Rv2569c exhibited cell wall–associated serine protease activity. Furthermore, Rv2569c was capable of degrading a range of protein substrates, including casein, fibrinogen, fibronectin, and E-cadherin. We also determined that the optimal conditions for the protease activity of Rv2569c occurred at a temperature of 37°C and a pH of 9.0, in the presence of MgCl2. To investigate the function of Rv2569c in M.tb, a deletion mutant of Rv2569c and its complemented strains were generated and used to infect A549 cells and mice. The results of the A549-cell infection experiments revealed that Rv2569c had the ability to cleave E-cadherin and facilitate the transmigration of M.tb through polarized A549 epithelial cell layers. Furthermore, in vivo infection assays demonstrated that Rv2569c could disrupt E-cadherin, enhance the colonization of M.tb, and induce pathological damage in the lungs of C57BL/6 mice. Collectively, these results strongly suggest that M.tb employs the serine protease Rv2569c to disrupt epithelial defenses and facilitate its systemic dissemination by crossing the epithelial barrier.

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Section: Discussionmentioning

confidence: 99%