![]() ![]() The aqueous phase was separated after centrifugation (12,000 × g), followed by the addition of isopropanol (660 μl). The pellet was resuspended in 1 ml of TRIzol ™ and 260 μl of chloroform was added. interrogans serovar Copenhageni with a concentration of 5 × 10 8 cell/ml were centrifuged at 2,000 × g. The in vitro assays with the recombinant protein point to a probable multifunctional role of LIC13086 during the infection process of leptospirosis.Ĭultures of virulent or culture-attenuated L. In the present work, we characterize a novel leptospiral outer membrane protein encoded by the gene LIC13086, and evaluate its ability to bind human extracellular matrix and plasma components. Furthermore, several leptospiral surface proteins interact with regulators and components of the host complement system as a mechanism of innate immune evasion ( Siqueira et al., 2017 Cavenague et al., 2019 Kochi et al., 2019 Passalia et al., 2020a). Surface exposed protein in leptospires can interact with human fibrinogen leading to a partial inhibition of fibrin clot formation thus facilitating the dissemination ( Oliveira et al., 2013 Fernandes et al., 2015). This bacterial surface-associated plasmin functions as a mechanism of degradation of several host components, immune evasion, and dissemination ( Vieira et al., 2009 Vieira et al., 2011 Vieira et al., 2012 Vieira et al., 2013 Vieira and Nascimento, 2016). Leptospires bind to the zymogen plasminogen, which is converted into plasmin ( Vieira et al., 2012). When leptospires reach the bloodstream, they are able to interact with circulating host plasma components ( Vieira et al., 2020). This step is mediated by leptospiral outer membrane adhesins, of which several were already characterized ( Vieira et al., 2014 Figueredo et al., 2017 Pereira et al., 2017 Cavenague et al., 2019 Kochi et al., 2019 Rossini et al., 2019 Passalia et al., 2020a). The initial process of infection consists of leptospires’ adhesion onto extracellular matrix molecules in the host epithelial skin tissue. These include leptospirosis-associated severe pulmonary hemorrhage syndrome ( Trevejo et al., 1998) and Weil’s disease ( Levett, 2001). In some cases, leptospirosis progresses to severe conditions characterized by jaundice, hemorrhages, hypotension, and multiple organ failure. Early symptoms of leptospirosis are unspecific and include fever, headaches, mild and muscle aches, and are commonly misdiagnosed by other febrile diseases. Humans are infected mainly via cuts and abrasions on the skin when exposed to contaminated soil or water ( Ko et al., 2009). Leptospires colonize their kidneys and are excreted alive in the environment. The synanthropic rodents Rattus rattus and Rattus norvegicus are the main urban reservoirs of the bacteria, being chronic asymptomatic carriers. Leptospirosis is caused by pathogenic Gram-negative bacteria of the genus Leptospira, which are classified in more than 90 genetic species and divided serologically into more than 300 serovars ( Vincent et al., 2019). It’s estimated more than one million cases and approximately 60 thousand deaths worldwide every year ( Costa et al., 2015). Human leptospirosis is an emerging neglected disease and occurs mainly in tropical and subtropical regions where the transmission conditions are appropriate. Taken together, our results suggest that the protein LIC13086 may have a multifunctional role in leptospiral pathogenesis, participating in host invasion, dissemination, and immune evasion processes. The newly characterized protein can also bind molecules of the complement system and the regulator C4BP and, thus, might have a role in the evasion mechanism of Leptospira. Also, by interacting with fibrinogen and plasma fibronectin, the protein LIC13086 probably has an inhibitory effect in the fibrin clot formation during the infection process. The recombinant protein LIC13086 can interact with the extracellular matrix component laminin and bind plasminogen, thus possibly participating during the adhesion process and dissemination. Here, we describe a novel leptospiral protein encoded by the gene LIC13086 as an outer membrane protein. ![]() The molecular mechanisms of leptospirosis infection are complex, and it is becoming clear that leptospires express several functionally redundant proteins to invade, disseminate, and escape the host’s immune response. Leptospirosis is a neglected zoonosis, caused by pathogenic spirochetes bacteria of the genus Leptospira. ![]()
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