Information on the mechanism by which
Information on the mechanism by which parasite infections promote ECM degradation is limited (McKerrow et al., 1983; Andrade, 1994; Lu and Lai, 2013; Thibeaux et al., 2014). The interaction of plasminogen-plasmin with proteins of microorganisms, including bacteria, has been suggested to play a key role in the degradation of ECM, acting on several ECM proteins including fibronectin, laminin and thrombospondin (Bergmann et al., 2005; Bhattacharya et al., 2012; Singh et al., 2012; Grossi et al., 2016). Also in parasites, it has been proposed that loosening the ECM can facilitate parasite KT203 in the host tissues during early stages of infection, as well as its establishment in a final location (Singh et al., 2015; González-Miguel et al., 2015). We can speculate that degradation of the ECM could allow the cysticercus to grow and survive. The enolase-plasminogen interaction could be one (among others) of the mechanism used by the parasite. While the presence of enolase binding and activating Plg (in the presence of tPA) was documented in this study for the larval stage of T. solium, enolases and other promoters of Plg activation could also be present in the human infective stage (oncosphere), which could reach several host tissues and develop into the larval stage. Previous studies showed that enolase, among other proteins, are expressed in the proteome of T. solium activated oncospheres (Santivañez et al., 2010). Studies to ascertain whether enolase is involved in the degradation of extracellular matrices are ongoing. If involved, they could be a major factor contributing to the parasite establishment in host tissues. It is also conceivable that one of the isoforms of enolase in T. solium could be more involved than others in Plg-binding.
Conflict of interest
Acknowledgments This work was supported by grant from PAPIIT-UNAM IN211217 (RJB). Dolores Adriana Ayón Núñez is a doctoral student from Programa de Doctorado en Ciencias Biomédicas, Universidad Nacional Autónoma de México (UNAM) and received fellowship 280263 from CONACYT. We also thank Karel Estrada, Cristina Parada Colín, Patricia de la Torre, Beatriz Hernández Téllez, Nelly Villalobos, Omar Rangel-Rivera and Mariana López Filloy for technical support.
Introduction Pathogenic Leptospira species may cause leptospirosis, a highly frequent tropical disease that represents an important public health problem. These spirochetes have evolved virulence strategies to colonize a variety of hosts. During infection, they express membrane proteins capable of binding to extracellular matrix molecules and host cells , , , , , , , . Virulent Leptospira strains have also devised mechanisms to overcome the host\'s innate immune responses. It has been shown that they can resist complement-mediated killing by recruiting soluble complement regulators such as factor H (FH), C4b binding protein (C4BP) and vitronectin. In this way, they are able to control all steps of the complement cascade , , . Another interesting feature related to Leptospira virulence is its capacity to bind human plasminogen, which is converted to plasmin in the presence of the host\'s specific activators , . This key enzyme of the coagulation system targets a number of substrates, including fibrinogen, fibrin, complement proteins C3 and C5, vitronectin, osteocalcin, coagulation factors V, VIII and X, injury-induced aggregated proteins, protease-activated receptor 1 and some collagenases (reviewed in ). A number of Leptospira surface-exposed proteins have been shown to act as adhesins, invasins or evasins (reviewed in ). Alongside these outer membrane proteins, the involvement of moonlighting proteins in Leptospira pathogenesis has been evaluated in the last few years. This fascinating class of proteins is known to perform diverse and independent functions in a single organism, being found in different subcellular locations. To date, two Leptospira proteins displaying moonlighting activities have been described: elongation factor-thermal unstable (Ef-Tu), described as a ligand for host ECM molecules, plasminogen and complement FH , and the metabolic enzyme enolase, shown to interact with human plasminogen .