Abstract
Leptospirosis is a neglected zoonosis, caused by pathogenic spirochetes bacteria of the genus Leptospira. 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. Here, we describe a novel leptospiral protein encoded by the gene LIC13086 as an outer membrane protein. The recombinant protein LIC13086 can interact with the extracellular matrix component laminin and bind plasminogen, thus possibly participating during the adhesion process and dissemination. 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 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. 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.
Highlights
Human leptospirosis is an emerging neglected disease and occurs mainly in tropical and subtropical regions where the transmission conditions are appropriate
The analysis of the protein LIC13086 by bioinformatics revealed a domain of unknown function (DUF4842), which is present in the C-terminal portion of a large number of uncharacterized proteins in phylogenetically different organisms such as Bacteroides, Vibrio, Shewanella, and Leptospira
In whole-genome microarray experiments to evaluate the effects of temperature on gene expression in L. interrogans serovar Lai, the LIC13086 homolog (LA3867) exhibited a 9.8 fold-change upregulation when grown at 30°C and shifted overnight to 37°C, when compared to 30°C long-term culture, FIGURE 9 | Characterization of rLIC13086 interaction with complement system components. (A) rLIC13086 immobilized was co-incubated with C7, C8, or C9 (1 mg) and different concentrations of heparin (0–500 mg/ml) for 2 h at 37°C
Summary
Human leptospirosis is an emerging neglected disease and occurs mainly in tropical and subtropical regions where the transmission conditions are appropriate. The synanthropic rodents Rattus rattus and Rattus norvegicus are the main urban reservoirs of the bacteria, being chronic asymptomatic carriers. Leptospires colonize their kidneys and are excreted alive in the environment. Leptospirosis progresses to severe conditions characterized by jaundice, hemorrhages, hypotension, and multiple organ failure. These include leptospirosis-associated severe pulmonary hemorrhage syndrome (Trevejo et al, 1998) and Weil’s disease (Levett, 2001)
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